title: Smad2 mediates Activin/Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells.
abstract: 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.
authors.affiliation: The State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Fei
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhu
authors.forename: Kai
authors.initials: K
authors.lastname: Xia
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Li
authors.forename: Jing-Dong J
authors.initials: JD
authors.lastname: Han
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D026901:Membrane Transport Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D055457:Nodal Protein / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D055457:Nodal Protein; D034741:RNA, Small Interfering; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; C107762:tapasin; D028341:Activins