Homeobox protein NANOG: Difference between revisions

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{{dablink|See [[NANOG (computing)]] for the network operators' group.}}
{{Infobox_gene}}
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'''Homeobox protein''' NANOG is a [[Transcription (biology)|transcriptional]] factor that helps [[Embryonic stem cell|embryonic stem cells]] (ESCs) maintain [[Cell_potency#Pluripotency|pluripotency]] by suppressing cell determination factors. Therefore NANOG deletion will trigger differentiation of ESCs. There are many different types of cancer that are associated with NANOG. In humans, this protein is encoded by the ''NANOG'' [[gene]].<ref name="pmid12787504">{{cite journal | vauthors = Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S | title = The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells | journal = Cell | volume = 113 | issue = 5 | pages = 631–42 | date = May 2003 | pmid = 12787504 | doi = 10.1016/S0092-8674(03)00393-3 }}</ref><ref name="pmid12787505">{{cite journal | vauthors = Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A | title = Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells | journal = Cell | volume = 113 | issue = 5 | pages = 643–55 | date = May 2003 | pmid = 12787505 | doi = 10.1016/S0092-8674(03)00392-1 }}</ref>
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{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Nanog homeobox
| HGNCid = 20857
| Symbol = NANOG
| AltSymbols =;
| OMIM = 607937
| ECnumber =
| Homologene = 78027
| MGIid = 1919200
| GeneAtlas_image1 = PBB_GE_NANOG_220184_at_tn.png
| Function = {{GNF_GO|id=GO:0003700 |text = transcription factor activity}} {{GNF_GO|id=GO:0043565 |text = sequence-specific DNA binding}}  
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}}
| Process = {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0009790 |text = embryonic development}} {{GNF_GO|id=GO:0045595 |text = regulation of cell differentiation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 79923
    | Hs_Ensembl = ENSG00000111704
    | Hs_RefseqProtein = NP_079141
    | Hs_RefseqmRNA = NM_024865
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 12
    | Hs_GenLoc_start = 7833330
    | Hs_GenLoc_end = 7839738
    | Hs_Uniprot = Q9H9S0
    | Mm_EntrezGene = 71950
    | Mm_Ensembl = 
    | Mm_RefseqmRNA = XM_132755
    | Mm_RefseqProtein = XP_132755
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
{{SI}}
{{CMG}}


==Overview==
== Structure ==
'''NANOG''' (pron. nanOg) is a [[Transcription (genetics)|transcription]] factor critically involved with self-renewal of undifferentiated [[embryonic stem cell]]s.  
The human NANOG protein coded by the NANOG1 gene, consists of 305 amino acids and possesses 3 functional domains: the N-terminal domain, the C- terminal domain, and the conserved [[homeodomain]]<nowiki/> motif. The [[homeodomain]]<nowiki/> region facilitates DNA binding. The human Nanog 1 gene is located on chromosome 12, and the mRNA contains a 915 bp open reading frame (ORF) with 4 exons and 3 introns.<ref>{{cite journal | vauthors = Gawlik-Rzemieniewska N, Bednarek I | title = The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells | journal = Cancer Biology & Therapy | volume = 17 | issue = 1 | pages = 1–10 | date = 2015-11-30 | pmid = 26618281 | pmc = 4848008 | doi = 10.1080/15384047.2015.1121348 }}</ref>


==Background information==
The N-terminal region of human NANOG is rich in serine, threonine and proline residues, and the C-terminus contains a tryptophan-rich domain. The homeodomain in hNANOG ranges from residues 95 to 155. There are also additional NANOG genes (NANOG2, NANOG p8) which potentially effect ESCs' differentiation. Scientists have shown that NANOG1 is fundamental for self-renewal and pluripotency, and NONAG p8 is highly expressed in cancer cells.<ref>{{cite journal | vauthors = Zhang W, Sui Y, Ni J, Yang T | title = Nanog gene: A propeller for stemness in primitive stem cells | journal = International Journal of Biological Sciences | volume = 12 | issue = 11 | pages = 1372–1381 | date = 2016 | pmid = 27877089 | pmc = 5118783 | doi = 10.7150/ijbs.16349 }}</ref>
===Embryonic stem cells===
NANOG is a gene expressed in [[embryonic stem cell]]s (ESCs) and is thought to be a key factor in maintaining [[pluripotency]]. NANOG thought to function in concert with other factors such as [[Oct-4|POU5F1]] and [[SOX2]] to establish ESC identity. These cells offer an important area of study because of their ability to maintain pluripotency. In other words, these cells have the ability to become virtually any cell of any of the three germ layers ([[endoderm]], [[ectoderm]], [[mesoderm]]). It is for this reason that understanding the mechanisms that maintain a cell's pluripotency is critical for researchers to understand how stem cells work; and may lead to future advances in treating degenerative diseases.


===History===
== Function ==
Dr Ian Chambers (currently of the Institute for Stem Cell Research, The [[University of Edinburgh]], UK) who isolated the mouse Nanog gene said: "Nanog seems to be a master gene that makes embryonic stem cells grow in the laboratory. In effect this makes stem cells immortal. Being Scottish, I therefore chose the name after the [[Tir_na_n-Og|Tir nan Og legend]]."<ref>{{cite web |url=http://www.sciencedaily.com/releases/2003/06/030602024530.htm |title=ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth |accessdate=2007-07-26 |format= |work=}}</ref>
[[File:Transcription programs in stem cells..jpg|thumb|Transcription programs in embryonic stem cells]]
NANOG is a transcription factor in [[embryonic stem cell]]s (ESCs) and is thought to be a key factor in maintaining [[pluripotency]]. NANOG is thought to function in concert with other factors such as [[Oct-4|POU5F1 (Oct-4)]] and [[SOX2]] to establish ESC identity. These cells offer an important area of study because of their ability to maintain pluripotency. In other words, these cells have the ability to become virtually any cell of any of the three germ layers ([[endoderm]], [[ectoderm]], [[mesoderm]]). It is for this reason that understanding the mechanisms that maintain a cell's pluripotency is critical for researchers to understand how stem cells work, and may lead to future advances in treating degenerative diseases.


===Genes that code for NANOG===
Analysis of arrested embryos demonstrated that embryos express pluripotency marker genes such as [[Oct-4|POU5F1]], NANOG and [[Rex1]].  Derived human ESC lines also expressed specific pluripotency markers:
Analysis of arrested embryos demonstrated that embryos express pluripotency marker genes such as [[OCT4]], NANOG and REX1.  Derived human ESC lines also expressed specific pluripotency markers:
*TRA-1-60
*TRA-1-60
*TRA-1-81
*TRA-1-81
Line 66: Line 17:
*alkaline phosphatase
*alkaline phosphatase
*TERT
*TERT
*REX1
*[[Rex1]]
These markers allowed for the differentiation ''in vitro'' and ''in vivo'' conditions into derivatives of all three germ layers.  <ref>Zhang X, Stojkovic P., Przyborski S, Cooke M, Armstrong L, Lako M, Stojkovic M.  Derivation of human embryonic stem cells from developing and arrested embryos.  Stem Cells.[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16990582&query_hl=3&itool=pubmed_docsum]</ref>
POU5F1 ([[OCT4]]), TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 are also related genes all responsible for self-renewal and pluripotent differentiation.  <ref>{{cite journal |author=Li SS, Liu YH, Tseng CN, Chung TL, Lee TY, Singh S |title=Characterization and gene expression profiling of five new human embryonic stem cell lines derived in Taiwan |journal=Stem Cells Dev. |volume=15 |issue=4 |pages=532-55 |year=2006 |pmid=16978057 |doi=10.1089/scd.2006.15.532}}</ref>


===NANOG protein===
These markers allowed for the differentiation ''in vitro'' and ''in vivo'' conditions into derivatives of all three germ layers.<ref name="pmid16990582">{{cite journal | vauthors = Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M, Stojkovic M | title = Derivation of human embryonic stem cells from developing and arrested embryos | journal = Stem Cells | volume = 24 | issue = 12 | pages = 2669–76 | date = December 2006 | pmid = 16990582 | doi = 10.1634/stemcells.2006-0377 }}</ref>
Human NANOG protein (Accession number [http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=protein&val=153945816 NP_079141]) is a 305 amino acid protein with a conserved homeodomain motif that is localized to the nuclear component of cells. The homeodomain facilitates DNA binding.  


There are N-terminal, homeodomain, and C-terminal region in human NANOG protein. Like murine NANOG, N-terminal region of human NANOG is rich in Ser, Thr and Pro residues and C-terminus contains W repeats. The homeodomain in hNANOG ranges from a.a.95 to a.a 155. The conserved sequence of homeodomain are a.a. 99-100, 102, 106-107, 110, 114, 119, 121, 127-128, 132, 134, 138-140, 142-145, 147, 149, and 151-152.
[[Oct-4|POU5F1]], TDGF1 (CRIPTO), [[SALL4]], LECT1, and BUB1 are also related genes all responsible for self-renewal and pluripotent differentiation.<ref name="pmid16978057">{{cite journal | vauthors = Li SS, Liu YH, Tseng CN, Chung TL, Lee TY, Singh S | title = Characterization and gene expression profiling of five new human embryonic stem cell lines derived in Taiwan | journal = Stem Cells and Development | volume = 15 | issue = 4 | pages = 532–55 | date = August 2006 | pmid = 16978057 | doi = 10.1089/scd.2006.15.532 }}</ref>


==Current research==
The NANOG protein has been found to be a transcriptional activator for the [[Rex1]] promoter, playing a key role in sustaining [[Rex1]] expression. Knockdown of NANOG in [[embryonic stem cell]]s results in a reduction of [[Rex1]] expression, while forced expression of NANOG stimulates [[Rex1]] expression.<ref>{{cite journal | vauthors = Shi W, Wang H, Pan G, Geng Y, Guo Y, Pei D | title = Regulation of the pluripotency marker Rex-1 by Nanog and Sox2 | journal = The Journal of Biological Chemistry | volume = 281 | issue = 33 | pages = 23319–25 | date = August 2006 | pmid = 16714766 | pmc =  | doi = 10.1074/jbc.M601811200 }}</ref>


===Molecular biology===
Besides the effects of NANOG in the embryonic stages of life, ectopic expression of NANOG in the adult stem cells can restore the proliferation and differentiation potential that is lost due to organismal aging or cellular senescence.<ref>{{cite journal | vauthors = Shahini A, Choudhury D, Asmani M, Zhao R, Lei P, Andreadis ST | title = NANOG restores the impaired myogenic differentiation potential of skeletal myoblasts after multiple population doublings | journal = Stem Cell Research | volume = 26 | issue = | pages = 55–66 | date = January 2018 | pmid = 29245050 | pmc =  | doi = 10.1016/j.scr.2017.11.018 }}</ref><ref>{{cite journal | vauthors = Shahini A, Mistriotis P, Asmani M, Zhao R, Andreadis ST | title = NANOG Restores Contractility of Mesenchymal Stem Cell-Based Senescent Microtissues | journal = Tissue Engineering. Part A | volume = 23 | issue = 11-12 | pages = 535–545 | date = June 2017 | pmid = 28125933 | pmc =  | doi = 10.1089/ten.TEA.2016.0494 }}</ref><ref>{{cite journal | vauthors = Mistriotis P, Bajpai VK, Wang X, Rong N, Shahini A, Asmani M, Liang MS, Wang J, Lei P, Liu S, Zhao R, Andreadis ST | title = NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression | journal = Stem Cells | volume = 35 | issue = 1 | pages = 207–221 | date = January 2017 | pmid = 27350449 | pmc =  | doi = 10.1002/stem.2452 }}</ref><ref>{{cite journal | vauthors = Han J, Mistriotis P, Lei P, Wang D, Liu S, Andreadis ST | title = Nanog reverses the effects of organismal aging on mesenchymal stem cell proliferation and myogenic differentiation potential | journal = Stem Cells | volume = 30 | issue = 12 | pages = 2746–59 | date = December 2012 | pmid = 22949105 | pmc = 3508087 | doi = 10.1002/stem.1223 }}</ref><ref>{{cite journal | vauthors = Münst B, Thier MC, Winnemöller D, Helfen M, Thummer RP, Edenhofer F | title = Nanog induces suppression of senescence through downregulation of p27KIP1 expression | journal = Journal of Cell Science | volume = 129 | issue = 5 | pages = 912–20 | date = March 2016 | pmid = 26795560 | pmc = 4813312 | doi = 10.1242/jcs.167932 }}</ref>
Overexpression of Nanog in mouse embryonic stem cells causes them to self-renew in the absence of [[Leukemia inhibitory factor]]. In the absence of Nanog, mouse embryonic stem cells differentiate into visceral/parietal endoderm (Chambers et al, 2003 and Mitsui et al, 2003)


Loss of Nanog function causes differentiation of embryonic stem cells into other cell types (Lin et al, 2005).
== Clinical significance ==


NANOG overexpression in human embryonic stem cells enables their propagation for multiple passages during which the cells remain pluripotent.<ref>Darr H, Mayshar Y, Benvenisty N. Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. Development. 2006 Mar;133(6):1193-201.[http://dev.biologists.org/cgi/content/full/133/6/1193]</ref> Gene knockdown of Nanog promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal.<ref>Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ. High-efficiency RNA interference in human embryonic stem cells. Stem Cells. 2005 Mar;23(3):299-305.[http://stemcells.alphamedpress.org/cgi/content/full/23/3/299]</ref>
=== Cancer ===


It has been shown that the tumour suppressor [[p53]] binds to the promoter of ''NANOG'' and suppresses its expression after DNA damage in mouse embryonic stem cells. p53 can thus induce differentiation of embronic stem cells into other cell types which undergo efficient p53-dependent cell-cycle arrest and [[apoptosis]]. (Lin et al, 2005)
NANOG is highly expressed in cancer stem cells and may thus function as an oncogene to promote carcinogenesis. High expression of NANOG correlates with poor survival in cancer patients.<ref name="pmid26013997">{{cite journal | vauthors = Gong S, Li Q, Jeter CR, Fan Q, Tang DG, Liu B | title = Regulation of NANOG in cancer cells | journal = Molecular Carcinogenesis | volume = 54 | issue = 9 | pages = 679–87 | date = September 2015 | pmid = 26013997 | pmc = 4536084 | doi = 10.1002/mc.22340 }}</ref><ref name="pmid25821200">{{cite journal | vauthors = Jeter CR, Yang T, Wang J, Chao HP, Tang DG | title = Concise Review: NANOG in Cancer Stem Cells and Tumor Development: An Update and Outstanding Questions | journal = Stem Cells | volume = 33 | issue = 8 | pages = 2381–90 | date = August 2015 | pmid = 25821200 | pmc = 4509798 | doi = 10.1002/stem.2007 }}</ref><ref name="pmid26618281">{{cite journal | vauthors = Gawlik-Rzemieniewska N, Bednarek I | title = The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells | journal = Cancer Biology & Therapy | volume = 17 | issue = 1 | pages = 1–10 | year = 2016 | pmid = 26618281 | pmc = 4848008 | doi = 10.1080/15384047.2015.1121348 }}</ref>


Nanog transforms [[3T3 cells|NIH3T3 cells]]. By using [[DNA microarray]] to find the transcription targets of Nanog, Nanog regulated genes have been identified . Some of these target genes explain the [[transformation]] of NIH3T3 cells. (Piestun et al, 2006)
Recent researches has shown that the localization of NANOG and other transcription factors have potential consequences on cellular function. Experimental evidence has shown that the level of NANOG p8 expression is elevated specially in cancer cells, which mean that NANOG p8 gene is a critical member in (CSCs) Cancer stem cells, so knocking it down could reduce the cancer malignancy.<ref>{{cite journal | vauthors = Zhang W, Sui Y, Ni J, Yang T | title = Nanog gene: A propeller for stemness in primitive stem cells | journal = International Journal of Biological Sciences | volume = 12 | issue = 11 | pages = 1372–1381 | date = 2016 | pmid = 27877089 | pmc = 5118783 | doi = 10.7150/ijbs.16349 }}</ref>


GATA6 and Nanog have been linked due to the similar cellular differentiation of ES cells in their absence, which leads to the hypothesis that Nanog may prevent ectodermal growth via repressing GATA6.<ref>Yates A, Chambers I. The homeodomain protein Nanog and pluripotency in mouse embryonic stem cells. Biochem Soc Trans. 2005 Dec;33 (Pt 6):1518-21 [http://www.biochemsoctrans.org/bst/033/1518/bst0331518.htm]</ref>
=== Diagnostics ===


Yamanaka et al., demonstrate [[Induced Pluripotent Stem Cell|induction of pluripotent stem cells]] from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Of these four factors it has been shown that Nanog was dispensable for such induction in this cell system.<ref> Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell, Vol 126, 663-676, 25 August 2006.[http://www.cell.com/content/article/abstract?uid=PIIS0092867406009767]</ref>
NANOG p8 gene has been evaluated as a prognostic and predictive cancer biomarker.<ref name="pmid24375318">{{cite journal | vauthors = Iv Santaliz-Ruiz LE, Xie X, Old M, Teknos TN, Pan Q | title = Emerging role of nanog in tumorigenesis and cancer stem cells | journal = International Journal of Cancer | volume = 135 | issue = 12 | pages = 2741–8 | date = December 2014 | pmid = 24375318 | pmc = 4065638 | doi = 10.1002/ijc.28690 }}</ref>


===Clinical medicine===
== Cancer stem cells ==


NANOG may be useful in the [[immunohistochemical]] diagnosis of tumors. NANOG is expressed in [[germ cell]]s of the [[fetus]] and in some [[germ cell tumor]]s of the [[gonads]]<ref>
Nanog is a [[transcription factor]] that controls both self-renewal and [[pluripotency]] of [[embryonic stem cell]]s. Similarly, the expression of Nanog family proteins is increased in many types of cancer and correlates with a worse prognosis.<ref>{{cite journal | vauthors = Zhang W, Sui Y, Ni J, Yang T | title = Nanog gene: A propeller for stemness in primitive stem cells | journal = International Journal of Biological Sciences | volume = 12 | issue = 11 | pages = 1372–1381 | date = 2016 | pmid = 27877089 | pmc = 5118783 | doi = 10.7150/ijbs.16349 }}</ref>
Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours.  Histopathology. 2005 Jul;47(1):48-56. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15982323&query_hl=28&itool=pubmed_docsum PubMed]</ref> and [[central nervous system]] (CNS).<ref name=Santagata>Santagata S, Hornick JL, Ligon KL. Comparative analysis of germ cell transcription factors in CNS germinoma reveals diagnostic utility of NANOG. Am J Surg Pathol. 2006 Dec;30(12):1613-8. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17122519&query_hl=28&itool=pubmed_docsum PubMed]</ref>  Among germ cell tumors, NANOG is expressed by [[seminoma]] and [[embryonal carcinoma]] but not by [[teratoma|mature teratoma]] nor [[endodermal sinus tumor]]<ref>
Hart AH, Hartley L, Parker K, Ibrahim M, Looijenga LH, Pauchnik M, Chow CW, Robb L.  The pluripotency homeobox gene NANOG is expressed in human germ cell tumors.  Cancer. 2005 Nov 15;104(10):2092-8. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16206293&query_hl=28&itool=pubmed_docsum PubMed]</ref>;  expression of NANOG by [[teratoma|immature teratoma]] and [[choriocarcinoma]] is unknown.  Among tumors usually found in the CNS, NANOG is expressed by [[germinoma]] (a germ cell tumor histologically identical to [[seminoma]] and [[dysgerminoma]]) but not by [[pineoblastoma]], [[lymphoma]], [[pituitary adenoma]] and [[glioma]]s;<ref name=Santagata/>  expression of NANOG by other germ cell tumors of the CNS is unknown.


==See also==
== Evolution ==
*[[Enhancer]]
[[Human|Humans]]<nowiki/> and [[Chimpanzee|chimpanzees]]<nowiki/> share ten NANOG [[Pseudogene|pseudogenes]] (NanogP2-P11) during evaluation, two of them are located on the X chromosome and they characterized by the 5’ promoter sequences and the absence of introns as a result of mRNA retrotransposition<ref>{{cite journal | vauthors = Gawlik-Rzemieniewska N, Bednarek I | title = The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells | journal = Cancer Biology & Therapy | volume = 17 | issue = 1 | pages = 1–10 | date = 2015-11-30 | pmid = 26618281 | pmc = 4848008 | doi = 10.1080/15384047.2015.1121348 }}</ref> all in the same places: one duplication pseudogene and nine retropseudogenes. Of the nine shared NANOG retropseudogenes, two lack the [[Polyadenylation|poly-(A) tails]]<nowiki/> characteristic of most retropseudogenes, indicating that copying errors occurred during their creation. Due to the high improbability that the same pseudogenes (copying errors included) would exist in the same places in two unrelated [[Genome|genomes]], [[Evolutionary biology|evolutionary biologists]] point to NANOG and its pseudogenes as providing [[evidence of common descent]] between humans and chimpanzees.<ref name="isbn1-59102-564-83">{{cite book|url=|title=Relics of Eden: The Powerful Evidence of Evolution in Human DNA|author=Daniel J. Fairbanks|publisher=Prometheus Books|others=|year=2007|isbn=1-59102-564-8|editor=|edition=|location=Buffalo, N.Y|pages=94–96, 177–182|doi=|oclc=|quote=|authorlink=|access-date=|origyear=}}</ref>
 
== Name ==
 
The name NANOG derives from [[Tir na n-Og|Tír na nÓg]] (Irish for "Land of the Young"), a name given to the Celtic Otherworld in Irish and Scottish mythology.<ref>{{cite web|url=https://www.sciencedaily.com/releases/2003/06/030602024530.htm|title=ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth|work=|access-date=2007-07-26}}</ref><ref>{{cite journal | vauthors = Gawlik-Rzemieniewska N, Bednarek I | title = The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells | journal = Cancer Biology & Therapy | volume = 17 | issue = 1 | pages = 1–10 | date = 2015-11-30 | pmid = 26618281 | pmc = 4848008 | doi = 10.1080/15384047.2015.1121348 }}</ref> Residents of Tír na nÓg are described as having eternal health and youth, hence the connection to the NANOG protein. 
 
== See also ==
*[[Enhancer (genetics)|Enhancer]]
*[[Histone]]
*[[Histone]]
*[[Oct-4]]
*[[Oct-4]]
*[[Pribnow box]]
*[[Pribnow box]]
*[[Promoter]]
*[[promoter (biology)|Promoter]]
*[[RNA polymerase]]
*[[RNA polymerase]]
*[[Brachyury]]
*[[Brachyury]]
Line 109: Line 61:
*[[Gene regulatory network]]
*[[Gene regulatory network]]
*[[Bioinformatics]]
*[[Bioinformatics]]
*[[PubMed|NANOG]]


==Sources==
== References ==
{{reflist|30em}}


*[http://www.nytimes.com/2005/09/13/health/13cell.html New York Times] "He has now applied the technique to human cells, starting with embryonic stem cells. The cells, he and colleagues say in the current issue of Cell, are controlled by a triumvirate of three transcription factors, known as '''oct4, sox2 and nanog'''.
== Further reading ==
*[http://www.wi.mit.edu/research/summaries/jaenisch.html MIT] "The transcription factors Oct4, Sox2, and Nanog have essential roles in early development and are required for the propagation of undifferentiated embryonic stem (ES) cells in culture. To gain insights into transcriptional regulation of human ES cells, we have, in collaboration with the Young lab, identified Oct4, Sox2, and Nanog target genes using genome-scale location analysis. We found, surprisingly, that Oct4, Sox2, and Nanog co-occupy a substantial portion of their target genes. These target genes frequently encode transcription factors, many of which are developmentally important homeodomain proteins. Our data also show that Oct4, Sox2, and Nanog collaborate to form regulatory circuitry in ES cells consisting of autoregulatory and feedforward loops."
{{refbegin | 2}}
*[http://jura.wi.mit.edu/young_public/hESregulation/index.html Young Lab- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells]
* {{cite journal | vauthors = Cavaleri F, Schöler HR | title = Nanog: a new recruit to the embryonic stem cell orchestra | journal = Cell | volume = 113 | issue = 5 | pages = 551–2 | date = May 2003 | pmid = 12787492 | doi = 10.1016/S0092-8674(03)00394-5 }}
* Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S and Smith A. Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell May 30;113(5):643-55 (2003).
* {{cite journal | vauthors = Constantinescu S | title = Stemness, fusion and renewal of hematopoietic and embryonic stem cells | journal = Journal of Cellular and Molecular Medicine | volume = 7 | issue = 2 | pages = 103–12 | year = 2004 | pmid = 12927049 | doi = 10.1111/j.1582-4934.2003.tb00209.x }}
* Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M and Yamanaka S. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell May 30;113(5):631-42 (2003)
* {{cite journal | vauthors = Pan G, Thomson JA | title = Nanog and transcriptional networks in embryonic stem cell pluripotency | journal = Cell Research | volume = 17 | issue = 1 | pages = 42–9 | date = January 2007 | pmid = 17211451 | doi = 10.1038/sj.cr.7310125 }}
* Lin TX, Chao C, Saito S, et al. P53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. NATURE CELL BIOLOGY 7 (2): 165-U80 FEB 2005.
* {{cite journal | vauthors = Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S | title = The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells | journal = Cell | volume = 113 | issue = 5 | pages = 631–42 | date = May 2003 | pmid = 12787504 | doi = 10.1016/S0092-8674(03)00393-3 }}
* {{cite journal | vauthors = Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A | title = Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells | journal = Cell | volume = 113 | issue = 5 | pages = 643–55 | date = May 2003 | pmid = 12787505 | doi = 10.1016/S0092-8674(03)00392-1 }}
* {{cite journal | vauthors = Clark AT, Rodriguez RT, Bodnar MS, Abeyta MJ, Cedars MI, Turek PJ, Firpo MT, Reijo Pera RA | title = Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma | journal = Stem Cells | volume = 22 | issue = 2 | pages = 169–79 | year = 2004 | pmid = 14990856 | doi = 10.1634/stemcells.22-2-169 }}
* {{cite journal | vauthors = Hart AH, Hartley L, Ibrahim M, Robb L | title = Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human | journal = Developmental Dynamics | volume = 230 | issue = 1 | pages = 187–98 | date = May 2004 | pmid = 15108323 | doi = 10.1002/dvdy.20034 }}
* {{cite journal | vauthors = Booth HA, Holland PW | title = Eleven daughters of NANOG | journal = Genomics | volume = 84 | issue = 2 | pages = 229–38 | date = August 2004 | pmid = 15233988 | doi = 10.1016/j.ygeno.2004.02.014 }}
* {{cite journal | vauthors = Hatano SY, Tada M, Kimura H, Yamaguchi S, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T | title = Pluripotential competence of cells associated with Nanog activity | journal = Mechanisms of Development | volume = 122 | issue = 1 | pages = 67–79 | date = January 2005 | pmid = 15582778 | doi = 10.1016/j.mod.2004.08.008 }}
* {{cite journal | vauthors = Deb-Rinker P, Ly D, Jezierski A, Sikorska M, Walker PR | title = Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation | journal = The Journal of Biological Chemistry | volume = 280 | issue = 8 | pages = 6257–60 | date = February 2005 | pmid = 15615706 | doi = 10.1074/jbc.C400479200 }}
* {{cite journal | vauthors = Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ | title = High-efficiency RNA interference in human embryonic stem cells | journal = Stem Cells | volume = 23 | issue = 3 | pages = 299–305 | date = March 2005 | pmid = 15749924 | doi = 10.1634/stemcells.2004-0252 }}
* {{cite journal | vauthors = Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E | title = Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours | journal = Histopathology | volume = 47 | issue = 1 | pages = 48–56 | date = July 2005 | pmid = 15982323 | doi = 10.1111/j.1365-2559.2005.02182.x }}
* {{cite journal | vauthors = Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M | title = Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages | journal = Stem Cells | volume = 23 | issue = 8 | pages = 1035–43 | date = September 2005 | pmid = 15983365 | doi = 10.1634/stemcells.2005-0080 }}
* {{cite journal | vauthors = Oh JH, Do HJ, Yang HM, Moon SY, Cha KY, Chung HM, Kim JH | title = Identification of a putative transactivation domain in human Nanog | journal = Experimental & Molecular Medicine | volume = 37 | issue = 3 | pages = 250–4 | date = June 2005 | pmid = 16000880 | doi = 10.1038/emm.2005.33 }}
* {{cite journal | vauthors = Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA | title = Core transcriptional regulatory circuitry in human embryonic stem cells | journal = Cell | volume = 122 | issue = 6 | pages = 947–56 | date = September 2005 | pmid = 16153702 | pmc = 3006442 | doi = 10.1016/j.cell.2005.08.020 }}
* {{cite journal | vauthors = Kim JS, Kim J, Kim BS, Chung HY, Lee YY, Park CS, Lee YS, Lee YH, Chung IY | title = Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog | journal = Experimental & Molecular Medicine | volume = 37 | issue = 6 | pages = 601–7 | date = December 2005 | pmid = 16391521 | doi = 10.1038/emm.2005.73 }}
* {{cite journal | vauthors = Darr H, Mayshar Y, Benvenisty N | title = Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features | journal = Development | volume = 133 | issue = 6 | pages = 1193–201 | date = March 2006 | pmid = 16501172 | doi = 10.1242/dev.02286 }}
* {{cite journal | vauthors = Saunders A, Li D, Faiola F, Huang X, Fidalgo M, Guallar D, Ding J, Yang F, Xu Y, Zhou H, Wang J | title = Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming | journal = Stem Cell Reports | volume = 8 | issue = 5 | pages = 1115–1123 | date = May 2017 | pmid = 28457890 | doi = 10.1016/j.stemcr.2017.03.023 }}
{{refend}}


==Resources==
== External links ==
* {{MeshName|NANOG+protein,+human}}
* {{MeshName|NANOG+protein,+human}}
* {{MeshName|Nanog+protein,+mouse}}
* {{MeshName|Nanog+protein,+mouse}}
* {{FactorBook|NANOG}}
* {{cite web| url =http://jura.wi.mit.edu/young_public/hESregulation/index.html| title =Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells| author =| authorlink =| work =Young Lab| publisher =Whitehead Institute for Biomedical Research| pages =| archive-url =https://web.archive.org/web/20090628185523/http://jura.wi.mit.edu/young_public/hESregulation/index.html| archive-date =2009-06-28| quote =| access-date =2009-02-28| deadurl =yes| df =}}
* {{cite web | url = http://www.wi.mit.edu/research/summaries/jaenisch.html | title = Jaenisch Lab Research Summary | author = | authorlink = | work = | publisher = Whitehead Institute | pages = | quote = | access-date = 2009-02-28}}
* [http://www.wellcome.ac.uk/News/2009/News/WTX056296.htm Discovery reveals more about stem cells' immortality]


==Further reading==
{{Transcription factors|g3}}
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Cavaleri F, Schöler HR |title=Nanog: a new recruit to the embryonic stem cell orchestra. |journal=Cell |volume=113 |issue= 5 |pages= 551-2 |year= 2003 |pmid= 12787492 |doi=  }}
*{{cite journal  | author=Constantinescu S |title=Stemness, fusion and renewal of hematopoietic and embryonic stem cells. |journal=J. Cell. Mol. Med. |volume=7 |issue= 2 |pages= 103-12 |year= 2004 |pmid= 12927049 |doi=  }}
*{{cite journal  | author=Pan G, Thomson JA |title=Nanog and transcriptional networks in embryonic stem cell pluripotency. |journal=Cell Res. |volume=17 |issue= 1 |pages= 42-9 |year= 2007 |pmid= 17211451 |doi= 10.1038/sj.cr.7310125 }}
*{{cite journal  | author=Mitsui K, Tokuzawa Y, Itoh H, ''et al.'' |title=The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. |journal=Cell |volume=113 |issue= 5 |pages= 631-42 |year= 2003 |pmid= 12787504 |doi=  }}
*{{cite journal  | author=Chambers I, Colby D, Robertson M, ''et al.'' |title=Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. |journal=Cell |volume=113 |issue= 5 |pages= 643-55 |year= 2003 |pmid= 12787505 |doi=  }}
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Clark AT, Rodriguez RT, Bodnar MS, ''et al.'' |title=Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. |journal=Stem Cells |volume=22 |issue= 2 |pages= 169-79 |year= 2004 |pmid= 14990856 |doi=  }}
*{{cite journal  | author=Hart AH, Hartley L, Ibrahim M, Robb L |title=Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human. |journal=Dev. Dyn. |volume=230 |issue= 1 |pages= 187-98 |year= 2004 |pmid= 15108323 |doi= 10.1002/dvdy.20034 }}
*{{cite journal  | author=Booth HA, Holland PW |title=Eleven daughters of NANOG. |journal=Genomics |volume=84 |issue= 2 |pages= 229-38 |year= 2005 |pmid= 15233988 |doi= 10.1016/j.ygeno.2004.02.014 }}
*{{cite journal  | author=Hatano SY, Tada M, Kimura H, ''et al.'' |title=Pluripotential competence of cells associated with Nanog activity. |journal=Mech. Dev. |volume=122 |issue= 1 |pages= 67-79 |year= 2005 |pmid= 15582778 |doi= 10.1016/j.mod.2004.08.008 }}
*{{cite journal  | author=Deb-Rinker P, Ly D, Jezierski A, ''et al.'' |title=Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation. |journal=J. Biol. Chem. |volume=280 |issue= 8 |pages= 6257-60 |year= 2005 |pmid= 15615706 |doi= 10.1074/jbc.C400479200 }}
*{{cite journal  | author=Zaehres H, Lensch MW, Daheron L, ''et al.'' |title=High-efficiency RNA interference in human embryonic stem cells. |journal=Stem Cells |volume=23 |issue= 3 |pages= 299-305 |year= 2005 |pmid= 15749924 |doi= 10.1634/stemcells.2004-0252 }}
*{{cite journal  | author=Hoei-Hansen CE, Almstrup K, Nielsen JE, ''et al.'' |title=Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours. |journal=Histopathology |volume=47 |issue= 1 |pages= 48-56 |year= 2005 |pmid= 15982323 |doi= 10.1111/j.1365-2559.2005.02182.x }}
*{{cite journal  | author=Hyslop L, Stojkovic M, Armstrong L, ''et al.'' |title=Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. |journal=Stem Cells |volume=23 |issue= 8 |pages= 1035-43 |year= 2006 |pmid= 15983365 |doi= 10.1634/stemcells.2005-0080 }}
*{{cite journal  | author=Oh JH, Do HJ, Yang HM, ''et al.'' |title=Identification of a putative transactivation domain in human Nanog. |journal=Exp. Mol. Med. |volume=37 |issue= 3 |pages= 250-4 |year= 2005 |pmid= 16000880 |doi=  }}
*{{cite journal  | author=Boyer LA, Lee TI, Cole MF, ''et al.'' |title=Core transcriptional regulatory circuitry in human embryonic stem cells. |journal=Cell |volume=122 |issue= 6 |pages= 947-56 |year= 2005 |pmid= 16153702 |doi= 10.1016/j.cell.2005.08.020 }}
*{{cite journal  | author=Kim JS, Kim J, Kim BS, ''et al.'' |title=Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog. |journal=Exp. Mol. Med. |volume=37 |issue= 6 |pages= 601-7 |year= 2006 |pmid= 16391521 |doi=  }}
*{{cite journal  | author=Darr H, Mayshar Y, Benvenisty N |title=Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features. |journal=Development |volume=133 |issue= 6 |pages= 1193-201 |year= 2006 |pmid= 16501172 |doi= 10.1242/dev.02286 }}
}}
 
==References==
{{Reflist|2}}
 
{{Transcription factors}}
 


[[Category:Gene expression]]
[[Category:Gene expression]]
[[Category:Genes]]
[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Transcription factors]]
[[Category:Transcription factors]]
[[cs:Nanog]]
[[sk:Nanog]]
{{WH}}
{{WikiDoc Sources}}

Latest revision as of 15:43, 25 November 2018

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Orthologs
SpeciesHumanMouse
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Homeobox protein NANOG is a transcriptional factor that helps embryonic stem cells (ESCs) maintain pluripotency by suppressing cell determination factors. Therefore NANOG deletion will trigger differentiation of ESCs. There are many different types of cancer that are associated with NANOG. In humans, this protein is encoded by the NANOG gene.[1][2]

Structure

The human NANOG protein coded by the NANOG1 gene, consists of 305 amino acids and possesses 3 functional domains: the N-terminal domain, the C- terminal domain, and the conserved homeodomain motif. The homeodomain region facilitates DNA binding. The human Nanog 1 gene is located on chromosome 12, and the mRNA contains a 915 bp open reading frame (ORF) with 4 exons and 3 introns.[3]

The N-terminal region of human NANOG is rich in serine, threonine and proline residues, and the C-terminus contains a tryptophan-rich domain. The homeodomain in hNANOG ranges from residues 95 to 155. There are also additional NANOG genes (NANOG2, NANOG p8) which potentially effect ESCs' differentiation. Scientists have shown that NANOG1 is fundamental for self-renewal and pluripotency, and NONAG p8 is highly expressed in cancer cells.[4]

Function

File:Transcription programs in stem cells..jpg
Transcription programs in embryonic stem cells

NANOG is a transcription factor in embryonic stem cells (ESCs) and is thought to be a key factor in maintaining pluripotency. NANOG is thought to function in concert with other factors such as POU5F1 (Oct-4) and SOX2 to establish ESC identity. These cells offer an important area of study because of their ability to maintain pluripotency. In other words, these cells have the ability to become virtually any cell of any of the three germ layers (endoderm, ectoderm, mesoderm). It is for this reason that understanding the mechanisms that maintain a cell's pluripotency is critical for researchers to understand how stem cells work, and may lead to future advances in treating degenerative diseases.

Analysis of arrested embryos demonstrated that embryos express pluripotency marker genes such as POU5F1, NANOG and Rex1. Derived human ESC lines also expressed specific pluripotency markers:

  • TRA-1-60
  • TRA-1-81
  • SSEA4
  • alkaline phosphatase
  • TERT
  • Rex1

These markers allowed for the differentiation in vitro and in vivo conditions into derivatives of all three germ layers.[5]

POU5F1, TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 are also related genes all responsible for self-renewal and pluripotent differentiation.[6]

The NANOG protein has been found to be a transcriptional activator for the Rex1 promoter, playing a key role in sustaining Rex1 expression. Knockdown of NANOG in embryonic stem cells results in a reduction of Rex1 expression, while forced expression of NANOG stimulates Rex1 expression.[7]

Besides the effects of NANOG in the embryonic stages of life, ectopic expression of NANOG in the adult stem cells can restore the proliferation and differentiation potential that is lost due to organismal aging or cellular senescence.[8][9][10][11][12]

Clinical significance

Cancer

NANOG is highly expressed in cancer stem cells and may thus function as an oncogene to promote carcinogenesis. High expression of NANOG correlates with poor survival in cancer patients.[13][14][15]

Recent researches has shown that the localization of NANOG and other transcription factors have potential consequences on cellular function. Experimental evidence has shown that the level of NANOG p8 expression is elevated specially in cancer cells, which mean that NANOG p8 gene is a critical member in (CSCs) Cancer stem cells, so knocking it down could reduce the cancer malignancy.[16]

Diagnostics

NANOG p8 gene has been evaluated as a prognostic and predictive cancer biomarker.[17]

Cancer stem cells

Nanog is a transcription factor that controls both self-renewal and pluripotency of embryonic stem cells. Similarly, the expression of Nanog family proteins is increased in many types of cancer and correlates with a worse prognosis.[18]

Evolution

Humans and chimpanzees share ten NANOG pseudogenes (NanogP2-P11) during evaluation, two of them are located on the X chromosome and they characterized by the 5’ promoter sequences and the absence of introns as a result of mRNA retrotransposition[19] all in the same places: one duplication pseudogene and nine retropseudogenes. Of the nine shared NANOG retropseudogenes, two lack the poly-(A) tails characteristic of most retropseudogenes, indicating that copying errors occurred during their creation. Due to the high improbability that the same pseudogenes (copying errors included) would exist in the same places in two unrelated genomes, evolutionary biologists point to NANOG and its pseudogenes as providing evidence of common descent between humans and chimpanzees.[20]

Name

The name NANOG derives from Tír na nÓg (Irish for "Land of the Young"), a name given to the Celtic Otherworld in Irish and Scottish mythology.[21][22] Residents of Tír na nÓg are described as having eternal health and youth, hence the connection to the NANOG protein.

See also

References

  1. ↑ Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (May 2003). "The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells". Cell. 113 (5): 631–42. doi:10.1016/S0092-8674(03)00393-3. PMID 12787504.
  2. ↑ Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (May 2003). "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells". Cell. 113 (5): 643–55. doi:10.1016/S0092-8674(03)00392-1. PMID 12787505.
  3. ↑ Gawlik-Rzemieniewska N, Bednarek I (2015-11-30). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. PMC 4848008. PMID 26618281.
  4. ↑ Zhang W, Sui Y, Ni J, Yang T (2016). "Nanog gene: A propeller for stemness in primitive stem cells". International Journal of Biological Sciences. 12 (11): 1372–1381. doi:10.7150/ijbs.16349. PMC 5118783. PMID 27877089.
  5. ↑ Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M, Stojkovic M (December 2006). "Derivation of human embryonic stem cells from developing and arrested embryos". Stem Cells. 24 (12): 2669–76. doi:10.1634/stemcells.2006-0377. PMID 16990582.
  6. ↑ Li SS, Liu YH, Tseng CN, Chung TL, Lee TY, Singh S (August 2006). "Characterization and gene expression profiling of five new human embryonic stem cell lines derived in Taiwan". Stem Cells and Development. 15 (4): 532–55. doi:10.1089/scd.2006.15.532. PMID 16978057.
  7. ↑ Shi W, Wang H, Pan G, Geng Y, Guo Y, Pei D (August 2006). "Regulation of the pluripotency marker Rex-1 by Nanog and Sox2". The Journal of Biological Chemistry. 281 (33): 23319–25. doi:10.1074/jbc.M601811200. PMID 16714766.
  8. ↑ Shahini A, Choudhury D, Asmani M, Zhao R, Lei P, Andreadis ST (January 2018). "NANOG restores the impaired myogenic differentiation potential of skeletal myoblasts after multiple population doublings". Stem Cell Research. 26: 55–66. doi:10.1016/j.scr.2017.11.018. PMID 29245050.
  9. ↑ Shahini A, Mistriotis P, Asmani M, Zhao R, Andreadis ST (June 2017). "NANOG Restores Contractility of Mesenchymal Stem Cell-Based Senescent Microtissues". Tissue Engineering. Part A. 23 (11–12): 535–545. doi:10.1089/ten.TEA.2016.0494. PMID 28125933.
  10. ↑ Mistriotis P, Bajpai VK, Wang X, Rong N, Shahini A, Asmani M, Liang MS, Wang J, Lei P, Liu S, Zhao R, Andreadis ST (January 2017). "NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression". Stem Cells. 35 (1): 207–221. doi:10.1002/stem.2452. PMID 27350449.
  11. ↑ Han J, Mistriotis P, Lei P, Wang D, Liu S, Andreadis ST (December 2012). "Nanog reverses the effects of organismal aging on mesenchymal stem cell proliferation and myogenic differentiation potential". Stem Cells. 30 (12): 2746–59. doi:10.1002/stem.1223. PMC 3508087. PMID 22949105.
  12. ↑ Münst B, Thier MC, Winnemöller D, Helfen M, Thummer RP, Edenhofer F (March 2016). "Nanog induces suppression of senescence through downregulation of p27KIP1 expression". Journal of Cell Science. 129 (5): 912–20. doi:10.1242/jcs.167932. PMC 4813312. PMID 26795560.
  13. ↑ Gong S, Li Q, Jeter CR, Fan Q, Tang DG, Liu B (September 2015). "Regulation of NANOG in cancer cells". Molecular Carcinogenesis. 54 (9): 679–87. doi:10.1002/mc.22340. PMC 4536084. PMID 26013997.
  14. ↑ Jeter CR, Yang T, Wang J, Chao HP, Tang DG (August 2015). "Concise Review: NANOG in Cancer Stem Cells and Tumor Development: An Update and Outstanding Questions". Stem Cells. 33 (8): 2381–90. doi:10.1002/stem.2007. PMC 4509798. PMID 25821200.
  15. ↑ Gawlik-Rzemieniewska N, Bednarek I (2016). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. PMC 4848008. PMID 26618281.
  16. ↑ Zhang W, Sui Y, Ni J, Yang T (2016). "Nanog gene: A propeller for stemness in primitive stem cells". International Journal of Biological Sciences. 12 (11): 1372–1381. doi:10.7150/ijbs.16349. PMC 5118783. PMID 27877089.
  17. ↑ Iv Santaliz-Ruiz LE, Xie X, Old M, Teknos TN, Pan Q (December 2014). "Emerging role of nanog in tumorigenesis and cancer stem cells". International Journal of Cancer. 135 (12): 2741–8. doi:10.1002/ijc.28690. PMC 4065638. PMID 24375318.
  18. ↑ Zhang W, Sui Y, Ni J, Yang T (2016). "Nanog gene: A propeller for stemness in primitive stem cells". International Journal of Biological Sciences. 12 (11): 1372–1381. doi:10.7150/ijbs.16349. PMC 5118783. PMID 27877089.
  19. ↑ Gawlik-Rzemieniewska N, Bednarek I (2015-11-30). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. PMC 4848008. PMID 26618281.
  20. ↑ Daniel J. Fairbanks (2007). Relics of Eden: The Powerful Evidence of Evolution in Human DNA. Buffalo, N.Y: Prometheus Books. pp. 94–96, 177–182. ISBN 1-59102-564-8.
  21. ↑ "ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth". Retrieved 2007-07-26.
  22. ↑ Gawlik-Rzemieniewska N, Bednarek I (2015-11-30). "The role of NANOG transcriptional factor in the development of malignant phenotype of cancer cells". Cancer Biology & Therapy. 17 (1): 1–10. doi:10.1080/15384047.2015.1121348. PMC 4848008. PMID 26618281.

Further reading

  • Cavaleri F, Schöler HR (May 2003). "Nanog: a new recruit to the embryonic stem cell orchestra". Cell. 113 (5): 551–2. doi:10.1016/S0092-8674(03)00394-5. PMID 12787492.
  • Constantinescu S (2004). "Stemness, fusion and renewal of hematopoietic and embryonic stem cells". Journal of Cellular and Molecular Medicine. 7 (2): 103–12. doi:10.1111/j.1582-4934.2003.tb00209.x. PMID 12927049.
  • Pan G, Thomson JA (January 2007). "Nanog and transcriptional networks in embryonic stem cell pluripotency". Cell Research. 17 (1): 42–9. doi:10.1038/sj.cr.7310125. PMID 17211451.
  • Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, Maruyama M, Maeda M, Yamanaka S (May 2003). "The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells". Cell. 113 (5): 631–42. doi:10.1016/S0092-8674(03)00393-3. PMID 12787504.
  • Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A (May 2003). "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells". Cell. 113 (5): 643–55. doi:10.1016/S0092-8674(03)00392-1. PMID 12787505.
  • Clark AT, Rodriguez RT, Bodnar MS, Abeyta MJ, Cedars MI, Turek PJ, Firpo MT, Reijo Pera RA (2004). "Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma". Stem Cells. 22 (2): 169–79. doi:10.1634/stemcells.22-2-169. PMID 14990856.
  • Hart AH, Hartley L, Ibrahim M, Robb L (May 2004). "Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human". Developmental Dynamics. 230 (1): 187–98. doi:10.1002/dvdy.20034. PMID 15108323.
  • Booth HA, Holland PW (August 2004). "Eleven daughters of NANOG". Genomics. 84 (2): 229–38. doi:10.1016/j.ygeno.2004.02.014. PMID 15233988.
  • Hatano SY, Tada M, Kimura H, Yamaguchi S, Kono T, Nakano T, Suemori H, Nakatsuji N, Tada T (January 2005). "Pluripotential competence of cells associated with Nanog activity". Mechanisms of Development. 122 (1): 67–79. doi:10.1016/j.mod.2004.08.008. PMID 15582778.
  • Deb-Rinker P, Ly D, Jezierski A, Sikorska M, Walker PR (February 2005). "Sequential DNA methylation of the Nanog and Oct-4 upstream regions in human NT2 cells during neuronal differentiation". The Journal of Biological Chemistry. 280 (8): 6257–60. doi:10.1074/jbc.C400479200. PMID 15615706.
  • Zaehres H, Lensch MW, Daheron L, Stewart SA, Itskovitz-Eldor J, Daley GQ (March 2005). "High-efficiency RNA interference in human embryonic stem cells". Stem Cells. 23 (3): 299–305. doi:10.1634/stemcells.2004-0252. PMID 15749924.
  • Hoei-Hansen CE, Almstrup K, Nielsen JE, Brask Sonne S, Graem N, Skakkebaek NE, Leffers H, Rajpert-De Meyts E (July 2005). "Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours". Histopathology. 47 (1): 48–56. doi:10.1111/j.1365-2559.2005.02182.x. PMID 15982323.
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External links

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