Volume 20, No 12, Dec 2010
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 20 Issue 12, December 2010: 1306-1318
ORIGINAL ARTICLES
Smad2 mediates Activin/Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells
Teng Fei1, Shanshan Zhu2, Kai Xia2, Jianping Zhang1, Zhongwei Li1, Jing-Dong J Ha2,3 and Ye-Guang Chen1
1The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2CAS Key Laboratory of Molecular Developmental Biology and Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China
3CAS Key Laboratory for Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China
Correspondence: Ye-Guang Chen, Jing-Dong J Han,(ygchen@tsinghua.edu.cn; jdhan@genetics.ac.cn)
Although Activin/Nodal signaling regulates pluripotency of human embryonic stem (ES) cells, how this signaling acts in mouse ES cells remains largely unclear. To investigate this, we confirmed that mouse ES cells possess active Smad2-mediated Activin/Nodal signaling and found that Smad2-mediated Activin/Nodal signaling is dispensable for self-renewal maintenance but is required for proper differentiation toward the mesendoderm lineage. To gain insights into the underlying mechanisms, Smad2-associated genes were identified by genome-wide chromatin immunoprecipitation-chip analysis. The results showed that there is a transcriptional correlation between Smad2 binding and Activin/Nodal signaling modulation, and that the development-related genes were enriched among the Smad2-bound targets. We further identified Tapbp as a key player in mesendoderm differentiation of mouse ES cells acting downstream of the Activin/Nodal-Smad2 pathway. Taken together, our findings suggest that Smad2-mediated Activin/Nodal signaling orchestrates mesendoderm lineage commitment of mouse ES cells through direct modulation of corresponding developmental regulator expression.
Cell Research (2010) 20:1306-1318. doi:10.1038/cr.2010.158; published online 16 November 2010
FULL TEXT | PDF
Browse 2324
