BMP induces cochlin expression to facilitate self-renewal and suppress neural differentiation of mouse embryonic stem cells.
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.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Jianping
J
Zhang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Teng
T
Fei
State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Zhongwei
Z
Li
State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Gaoyang
G
Zhu
State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Lu
L
Wang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: ygchen@tsinghua.edu.cn.
Ye-Guang
YG
Chen
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D055415:Bone Morphogenetic Protein 4 / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016384:Consensus Sequence; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology*; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation; D015854:Up-Regulation
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; C491729:Coch protein, mouse; D016326:Extracellular Matrix Proteins; D034741:RNA, Small Interfering; D051785:Smad Proteins; D048049:Extracellular Signal-Regulated MAP Kinases