Homeobox protein NANOG: Difference between revisions

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{{dablink|See [[NANOG (computing)]] for the network operators' group.}}
{{dablink|See [[NANOG (computing)]] for the network operators' group.}}
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{{Infobox_gene}}
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'''NANOG''' (pron. nanOg) is a [[Transcription (genetics)|transcription]] factor critically involved with self-renewal of undifferentiated [[embryonic stem cell]]s. 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.  
Human NANOG protein  is a 305 amino acid protein with a conserved homeodomain motif that is localized to the nuclear component of cells. The [[homeodomain]] region facilitates DNA binding.


==Background information==
There are N-terminal, [[homeodomain]], and C-terminal regions in human NANOG protein. Like murine NANOG, the N-terminal region of human NANOG is rich in Ser, Thr and Pro residues, and the C-terminus contains W repeats. The homeodomain in hNANOG ranges from residues 95 to 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.
===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 18:
*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 = Dec 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 = Aug 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 = Aug 2006 | pmid = 16714766 | pmc =  | doi = 10.1074/jbc.M601811200 }}</ref>


===Molecular biology===
== Clinical significance ==
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).
=== Cancer ===


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>
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 | year = 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 (Dayton, Ohio) | volume = 33 | issue = 8 | pages = 2381–90 | year = 2015 | pmid = 25821200 | pmc = 4509798 | doi = 10.1002/stem.2007 | url = }}</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>


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)
=== Diagnostics ===


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)
NANOG 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 | year = 2014 | pmid = 24375318 | pmc = 4065638 | doi = 10.1002/ijc.28690 }}</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>
== Evolution ==


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>
[[Human]]s and [[chimpanzee]]s share ten NANOG [[pseudogene]]s, all in the same places:  one duplication pseudogene and nine retropseudogenes. Of the nine shared NANOG retropseudogenes, two lack the [[Polyadenylation|poly-(A) tail]]s characteristic of most retropseudogenes, indicating 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]]s, [[Evolutionary biology|evolutionary biologists]] point to NANOG and its pseudogenes as providing formidable [[evidence of common descent]] between humans and chimpanzees.<ref name="isbn1-59102-564-8">{{cite book | author = Daniel J. Fairbanks | authorlink = | editor = | others = | title = Relics of Eden: The Powerful Evidence of Evolution in Human DNA | edition = | publisher = Prometheus Books | location = Buffalo, N.Y | year = 2007 | origyear = | pages = 94–96, 177–182 | quote = | isbn = 1-59102-564-8 | oclc = | doi = | url = | accessdate = }}</ref>


===Clinical medicine===
== Name ==


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>
Professor Ian Chambers (currently of the [[MRC Centre for Regenerative Medicine]], 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|Tír na nÓg 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 |work=}}</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==
== See also ==
*[[Enhancer]]
*[[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 55:
*[[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 = Jan 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 = Aug 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 = Jan 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 = Feb 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 = Mar 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 = Jul 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 = Sep 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 = Jun 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 = Sep 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 = Dec 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 = Mar 2006 | pmid = 16501172 | doi = 10.1242/dev.02286 }}
* {{cite journal | vauthors = Saunders A, Wang J | title = Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming| journal = Stem Cell Reports | date = Mar 2006 | 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 =| archiveurl =https://web.archive.org/web/20090628185523/http://jura.wi.mit.edu/young_public/hESregulation/index.html| archivedate =2009-06-28| quote =| accessdate =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 = | accessdate = 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:Human genes]]
[[Category:Oncology]]
[[Category:Transcription factors]]
[[Category:Transcription factors]]
[[cs:Nanog]]
[[sk:Nanog]]
{{WH}}
{{WikiDoc Sources}}

Revision as of 03:55, 2 December 2017

See NANOG (computing) for the network operators' group.
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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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View/Edit Human

NANOG (pron. nanOg) is a transcription factor critically involved with self-renewal of undifferentiated embryonic stem cells. In humans, this protein is encoded by the NANOG gene.[1][2]

Structure

Human NANOG protein is a 305 amino acid protein with a conserved homeodomain motif that is localized to the nuclear component of cells. The homeodomain region facilitates DNA binding.

There are N-terminal, homeodomain, and C-terminal regions in human NANOG protein. Like murine NANOG, the N-terminal region of human NANOG is rich in Ser, Thr and Pro residues, and the C-terminus contains W repeats. The homeodomain in hNANOG ranges from residues 95 to 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.

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.[3]

POU5F1, TDGF1 (CRIPTO), SALL4, LECT1, and BUB1 are also related genes all responsible for self-renewal and pluripotent differentiation.[4]

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.[5]

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.[6][7][8]

Diagnostics

NANOG has been evaluated as a prognostic and predictive cancer biomarker.[9]

Evolution

Humans and chimpanzees share ten NANOG pseudogenes, 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 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 formidable evidence of common descent between humans and chimpanzees.[10]

Name

Professor Ian Chambers (currently of the MRC Centre for Regenerative Medicine, 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 Tír na nÓg legend."[11]

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. ↑ Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M, Stojkovic M (Dec 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.
  4. ↑ Li SS, Liu YH, Tseng CN, Chung TL, Lee TY, Singh S (Aug 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.
  5. ↑ Shi W, Wang H, Pan G, Geng Y, Guo Y, Pei D (Aug 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.
  6. ↑ Gong S, Li Q, Jeter CR, Fan Q, Tang DG, Liu B (2015). "Regulation of NANOG in cancer cells". Molecular Carcinogenesis. 54 (9): 679–87. doi:10.1002/mc.22340. PMC 4536084. PMID 26013997.
  7. ↑ Jeter CR, Yang T, Wang J, Chao HP, Tang DG (2015). "Concise Review: NANOG in Cancer Stem Cells and Tumor Development: An Update and Outstanding Questions". Stem Cells (Dayton, Ohio). 33 (8): 2381–90. doi:10.1002/stem.2007. PMC 4509798. PMID 25821200.
  8. ↑ 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.
  9. ↑ Iv Santaliz-Ruiz LE, Xie X, Old M, Teknos TN, Pan Q (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.
  10. ↑ 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.
  11. ↑ "ScienceDaily: Cells Of The Ever Young: Getting Closer To The Truth". Retrieved 2007-07-26.

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 (Jan 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 (Aug 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 (Jan 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 (Feb 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 (Mar 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 (Jul 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.
  • Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M (Sep 2005). "Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages". Stem Cells. 23 (8): 1035–43. doi:10.1634/stemcells.2005-0080. PMID 15983365.
  • Oh JH, Do HJ, Yang HM, Moon SY, Cha KY, Chung HM, Kim JH (Jun 2005). "Identification of a putative transactivation domain in human Nanog". Experimental & Molecular Medicine. 37 (3): 250–4. doi:10.1038/emm.2005.33. PMID 16000880.
  • 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 (Sep 2005). "Core transcriptional regulatory circuitry in human embryonic stem cells". Cell. 122 (6): 947–56. doi:10.1016/j.cell.2005.08.020. PMC 3006442. PMID 16153702.
  • Kim JS, Kim J, Kim BS, Chung HY, Lee YY, Park CS, Lee YS, Lee YH, Chung IY (Dec 2005). "Identification and functional characterization of an alternative splice variant within the fourth exon of human nanog". Experimental & Molecular Medicine. 37 (6): 601–7. doi:10.1038/emm.2005.73. PMID 16391521.
  • Darr H, Mayshar Y, Benvenisty N (Mar 2006). "Overexpression of NANOG in human ES cells enables feeder-free growth while inducing primitive ectoderm features". Development. 133 (6): 1193–201. doi:10.1242/dev.02286. PMID 16501172.
  • Saunders A, Wang J (Mar 2006). "Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming". Stem Cell Reports. doi:10.1016/j.stemcr.2017.03.023.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Homeobox_protein_NANOG&oldid=1415591"