Abstract
BMP4 maintains self-renewal of mouse embryonic stem cells (ESCs) in collaboration with LIF. Here, we report the identification of a novel key BMP target gene, cochlin (Coch) in mouse ESCs. Coch can be significantly up-regulated by BMP4 specifically in ESCs but not in somatic differentiated cells, and this up-regulation is dependent on the BMP signaling mediators Smad1/5 and Smad4. Overexpression of Coch can partially substitute BMP4 to promote self-renewal of mouse ESCs together with LIF, whereas knockdown of Coch impairs self-renewal marker gene expression even in the presence of both BMP4 and LIF. Further studies showed that COCH could mimic BMP4 in repressing neural differentiation of mouse ESCs upon LIF withdrawal and the inhibitory effect of BMP4 on neural differentiation is compromised by Coch knockdown. Taken together, our data suggest that COCH is a part of the downstream target network of BMP signaling and serves as another important effector to fine-tune mouse ESC fates.
Highlights
BMP signaling can maintain self-renewal of mouse embryonic stem cells (ESCs) together with leukemia inhibitory factor (LIF)
BMP4 Up-regulates Coch Expression in ESCs—To identify direct downstream target genes of BMP signaling, we previously carried out Smad Chromatin Immunoprecipitation (ChIP)-chip and ChIP-seq combined with RNA expression microarray upon BMP4 stimulation in mouse ESCs [23]
We report that Coch is a BMP target and is involved in BMP-mediated pluripotency maintenance of mouse embryonic stem cells
Summary
Results: Cochlin is a target gene of BMP and supports self-renewal of mouse ESCs through suppressing neural differentiation. BMP4 maintains self-renewal of mouse embryonic stem cells (ESCs) in collaboration with LIF. Appropriate activity of extracellular signal-regulated kinase (ERK) within the cells plays a central role in the fate choices of mouse ESCs (10 –12). Besides these intrinsic factors, extracellular cytokines such as leukemia inhibitory factor (LIF), transforming growth factor  (TGF-) superfamily, and Wnt signaling have been shown to govern ESC fate [13,14,15]. We report the identification of cochlin (coagulation factor C homolog) (Coch), as another important direct target gene of BMP signaling, which promotes mouse ESC self-renewal by inhibition of neural differentiation
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