BMP Induction of Id Proteins Suppresses Differentiation and Sustains Embryonic Stem Cell Self-Renewal in Collaboration with STAT3

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.

Shh/BMP‐4 signaling pathway is essential for intestinal epithelial development during Xenopus larval‐to‐adult remodeling

“…The only result we obtained concerning epithelial proliferation is that excessive Chordin, that is, BMP-4 deficiency, results in the reduction of proliferation and the total number of adult progenitor cells. This finding suggests a possibility that a certain amount of BMP-4 may be essential for the maintenance and/or self-renewal of the intestinal stem cells, as proposed in other organs such as the ovary (Xie and Spradling, 1998;Fujiwara et al, 2001) and embryonic stem cells (Ying et al, 2003;Qi et al, 2004). To address its functions in the epithelial cell proliferation more precisely, further studies are necessary to distinguish effects of BMP-4 on stem cells from those on their descendant proliferating cells.…”

Evidence‐Based Theory for Integrated Genome Regulation of Ontogeny—An Unprecedented Role of Nuclear FGFR1 Signaling

“…Maintenance of the self‐renewing state of the mouse embryonic stem cells (ESCs), also requires the environmental factor cytokine, LIF, which activates STAT3 through phosphorylation and serum derived BMP4 which triggers Smad1 phosphorylation. BMP4, acts in conjunction with LIF to maintain the self‐renewal and pluripotency of mESC by activating the first cluster Oct4, Sox2, and Nanog cluster genes (Ying et al, 2003). Closely related to the pluripotency networks are Polycomb repressor SUZ12 and CTCF an insulator binding protein.…”

Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells

“…Several studies have pointed toward members of the inhibitor of DNA binding (Id) protein family, a class of helix-loop-helix (HLH) proteins, as important targets for BMP signalling [5][6][7][8]. HLH proteins act as transcriptional regulators and are essential factors for lymphoid development and function [9][10][11].…”