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BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3.

TitleBMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3.
Publication TypeJournal Article
Year of Publication2003
AuthorsYing QLong, Nichols J, Chambers I, Smith A
JournalCell
Volume115
Issue3
Pagination281-92
Date Published2003 Oct 31
ISSN0092-8674
KeywordsAnimals, Bone Morphogenetic Protein 4, Bone Morphogenetic Proteins, Cell Differentiation, Cell Division, Cell Lineage, Cells, Cultured, Culture Media, Serum-Free, DNA-Binding Proteins, Homeodomain Proteins, Inhibitor of Differentiation Protein 1, Interleukin-6, Leukemia Inhibitory Factor, Mice, Repressor Proteins, Signal Transduction, STAT3 Transcription Factor, Stem Cells, Trans-Activators, Transcription Factors
Abstract

The cytokine leukemia inhibitory factor (LIF) drives self-renewal of mouse embryonic stem (ES) cells by activating the transcription factor STAT3. In serum-free cultures, however, LIF is insufficient to block neural differentiation and maintain pluripotency. Here, we report that bone morphogenetic proteins (BMPs) act in combination with LIF to sustain self-renewal and preserve multilineage differentiation, chimera colonization, and germline transmission properties. ES cells can be propagated from single cells and derived de novo without serum or feeders using LIF plus BMP. The critical contribution of BMP is to induce expression of Id genes via the Smad pathway. Forced expression of Id liberates ES cells from BMP or serum dependence and allows self-renewal in LIF alone. Upon LIF withdrawal, Id-expressing ES cells differentiate but do not give rise to neural lineages. We conclude that blockade of lineage-specific transcription factors by Id proteins enables the self-renewal response to LIF/STAT3.

Alternate JournalCell
PubMed ID14636556