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The molecular basis of pluripotency in mouse embryonic stem cells.

TitleThe molecular basis of pluripotency in mouse embryonic stem cells.
Publication TypeJournal Article
Year of Publication2004
AuthorsChambers I
JournalCloning Stem Cells
Volume6
Issue4
Pagination386-91
Date Published2004
ISSN1536-2302
KeywordsAnimals, Bone Morphogenetic Proteins, Embryo, Mammalian, Gene Expression Regulation, Interleukin-6, Leukemia Inhibitory Factor, Mice, Pluripotent Stem Cells, Signal Transduction
Abstract

Mouse embryonic stem (ES) cell self-renewal depends upon extrinsic signals from leukemia inhibitory factor (LIF) and bone morphogenetic protein (BMP). These molecules activate, respectively, the nuclear localization of the latent transcription factor STAT3 and the expression of Id genes. In contrast, the homeodomain proteins Oct4 and the recently identified Nanog are intrinsic factors required for maintenance of the undifferentiated state. When overexpressed, Nanog allows ES cells to self-renew in the absence of the otherwise obligatory LIF and BMP signals. However, the highest efficiency of ES cell self-renewal occurs when Nanog is overexpressed and cells are exposed to LIF. In contrast, when Oct4 is overexpressed, ES cells differentiate in a similar manner to the differentiation that occurs upon LIF withdrawal. These observations are brought together to provide a genetic model of ES cell self-renewal centered upon interactions between Oct4, STAT3 and Nanog.

DOI10.1089/clo.2004.6.386
Alternate JournalCloning Stem Cells
PubMed ID15671667