Identification, cloning and expression analysis of the pluripotency promoting Nanog genes in mouse and human.
TLDR
The conservation in gene sequence, structure, and expression of mouse and human Nanog and Nanog2 genes may reflect a common role in the maintenance of pluripotency in both species.Abstract:
The murine Nanog gene, a member of the homeobox family of DNA binding transcription factors, has been shown recently to maintain pluripotency of embryonic stem cells. We have used a sequence homology and expression screen to identify and clone the mouse and human Nanog genes and characterized their phylogenetic context and expression patterns. We report here the gene structure and expression patterns of the mouse Nanog gene, the human Nanog and Nanog2 genes, and six processed human Nanog pseudogenes. Mouse Nanog expression is high in undifferentiated embryonic stem cells and is down-regulated during embryonic stem cell differentiation, concomitant with loss of pluripotency. Murine embryonic Nanog expression is detected in the inner cell mass of the blastocyst. After implantation, Nanog is detectable at embryonic day (E) 6 in proximal epiblast in the region of the presumptive primitive streak. Expression extends distally as the streak elongates during gastrulation and remains restricted to epiblast. Nanog RNA is down-regulated in cells ingressing through the streak to form mesoderm and definitive endoderm. Nanog expression also marks the pluripotent germ cells of the nascent gonad at E11.5–E12.5 and is highly expressed in germ cell tumour and teratoma-derived cell lines. Reverse transcriptase-polymerase chain reaction analysis detected mouse Nanog expression at low levels in several adult tissues. The human Nanog genes are expressed in embryonic stem cells and down-regulated in all adult tissues and differentiated cell lines examined. High levels of human Nanog expression were detected by Northern analysis in the undifferentiated N-Tera embryonal carcinoma cell line. The conservation in gene sequence, structure, and expression of mouse and human Nanog and Nanog2 genes may reflect a common role in the maintenance of pluripotency in both species. Developmental Dynamics 230:187–198, 2004. © 2004 Wiley-Liss, Inc.read more
Citations
More filters
Journal ArticleDOI
Core transcriptional regulatory circuitry in human embryonic stem cells.
Laurie A. Boyer,Tong Ihn Lee,Megan F. Cole,Sarah E. Johnstone,Stuart S. Levine,Jacob P. Zucker,Matthew G. Guenther,Roshan M. Kumar,Heather L. Murray,Richard G. Jenner,David K. Gifford,David K. Gifford,David K. Gifford,Douglas A. Melton,Douglas A. Melton,Rudolf Jaenisch,Richard A. Young,Richard A. Young +17 more
TL;DR: Insight is provided into the transcriptional regulation of stem cells and how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal and how they collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops.
Journal ArticleDOI
Naive and primed pluripotent states.
TL;DR: It is proposed that two phases of pluripotency can be defined: naive and primed, and this distinction extends to pluripotent stem cells derived from embryos or by molecular reprogramming ex vivo.
Journal ArticleDOI
Nanog safeguards pluripotency and mediates germline development.
Ian Chambers,José C. R. Silva,Douglas Colby,Jennifer Nichols,Jennifer Nichols,Bianca Nijmeijer,Morag Robertson,Jan Vrána,Kenneth Jones,Kenneth Jones,Lars Grotewold,Austin Smith +11 more
TL;DR: By genetic deletion, it is shown that, although they are prone to differentiate, embryonic stem cells can self-renew indefinitely in the permanent absence of Nanog, and it is surmised that Nanog stabilizes embryonicstem cells in culture by resisting or reversing alternative gene expression states.
Journal ArticleDOI
Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming
Rudolf Jaenisch,Richard A. Young +1 more
TL;DR: In this article, the authors review strategies to reprogram somatic cells to a pluripotent embryonic state and discuss their understanding of the molecular mechanisms of reprogramming based on recent insights into the regulatory circuitry of the PLSTM.
Journal ArticleDOI
Transcriptional regulation of nanog by OCT4 and SOX2.
David Rodda,Joon-Lin Chew,Joon-Lin Chew,Leng-Hiong Lim,Yuin-Han Loh,Yuin-Han Loh,Bei Wang,Huck-Hui Ng,Huck-Hui Ng,Paul Robson +9 more
TL;DR: By specific knockdown of Oct4 and Sox2 mRNA by RNA interference in embryonic stem cells, this work provides genetic evidence for a link between Oct4, Sox2, and the Nanog promoter, extending the understanding of the pluripotent genetic regulatory network within which the Sox2-Oct4 complex are at the top of the regulatory hierarchy.
References
More filters
Journal ArticleDOI
Pluripotency of mesenchymal stem cells derived from adult marrow
Yuehua Jiang,Balkrishna N. Jahagirdar,R. Lee Reinhardt,Robert E. Schwartz,C. Dirk Keene,Xilma R. Ortiz-Gonzalez,Morayma Reyes,Todd Lenvik,Troy C. Lund,Mark Blackstad,Jingbo Du,Sara Aldrich,Aaron Lisberg,Walter C. Low,David A. Largaespada,Catherine M. Verfaillie +15 more
TL;DR: It is reported here that cells co-purifying with mesenchymal stem cells—termed here multipotent adult progenitor cells or MAPCs—differentiate, at the single cell level, not only into meschymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro.
Journal ArticleDOI
Formation of Pluripotent Stem Cells in the Mammalian Embryo Depends on the POU Transcription Factor Oct4
Jennifer Nichols,Branko Zevnik,Konstantinos Anastassiadis,Hitoshi Niwa,Daniela Klewe-Nebenius,Ian Chambers,Hans R. Schöler,Austin Smith +7 more
TL;DR: It is reported that the activity of Oct4 is essential for the identity of the pluripotential founder cell population in the mammalian embryo and also determines paracrine growth factor signaling from stem cells to the trophectoderm.
Journal ArticleDOI
Functional expression cloning of nanog, a pluripotency sustaining factor in embryonic stem cells
Ian Chambers,Douglas Colby,Morag Robertson,Jennifer Nichols,Sonia Lee,Susan Tweedie,Austin Smith +6 more
TL;DR: These findings establish a central role for Nanog in the transcription factor hierarchy that defines ES cell identity and confirm that Cytokine dependence, multilineage differentiation, and embryo colonization capacity are fully restored upon transgene excision.
Journal ArticleDOI
The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells
Kaoru Mitsui,Yoshimi Tokuzawa,Hiroaki Itoh,Kohichi Segawa,Mirei Murakami,Kazutoshi Takahashi,Masayoshi Maruyama,Mitsuyo Maeda,Shinya Yamanaka +8 more
TL;DR: Nanog is a critical factor underlying pluripotency in both ICM and ES cells, and it is found that one of them, encoding the homeoprotein Nanog, was capable of maintaining ES cell self-renewal independently of LIF/Stat3.
Journal ArticleDOI
Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro.
TL;DR: The derivation of pluripotent embryonic stem (ES) cells from human blastocysts is described, providing a model to study early human embryology, an investigational tool for discovery of novel growth factors and medicines, and a potential source of cells for use in transplantation therapy.
Related Papers (5)
Core transcriptional regulatory circuitry in human embryonic stem cells.
Laurie A. Boyer,Tong Ihn Lee,Megan F. Cole,Sarah E. Johnstone,Stuart S. Levine,Jacob P. Zucker,Matthew G. Guenther,Roshan M. Kumar,Heather L. Murray,Richard G. Jenner,David K. Gifford,David K. Gifford,David K. Gifford,Douglas A. Melton,Douglas A. Melton,Rudolf Jaenisch,Richard A. Young,Richard A. Young +17 more