Open AccessTranscription Elongation Factor Tcea3 Regulates the Pluripotent Differentiation Potential of Mouse Embryonic Stem Cells Via the Lefty1 ‐Nodal‐Smad2 Pathway
Author(s) -
Park KyungSoon,
Cha Young,
Kim ChunHyung,
Ahn HeeJin,
Kim Dohoon,
Ko Sanghyeok,
Kim KyeoungHwa,
Chang MiYoon,
Ko JongHyun,
Noh YooSun,
Han YongMahn,
Kim Jonghwan,
Song Jihwan,
Kim Jin Young,
Tesar Paul J.,
Lanza Robert,
Lee KyungAh,
Kim KwangSoo
Publication year - 2013
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1284
Subject(s) - biology , induced pluripotent stem cell , microbiology and biotechnology , sox2 , embryonic stem cell , homeobox protein nanog , cellular differentiation , transcription factor , stem cell , rex1 , embryoid body , genetics , gene
Self‐renewal and pluripotency are hallmark properties of pluripotent stem cells, including embryonic stem cells (ESCs) and iPS cells. Previous studies revealed the ESC‐specific core transcription circuitry and showed that these core factors (e.g., Oct3/4 , Sox2 , and Nanog ) regulate not only self‐renewal but also pluripotent differentiation. However, it remains elusive how these two cell states are regulated and balanced during in vitro replication and differentiation. Here, we report that the transcription elongation factor Tcea3 is highly enriched in mouse ESCs (mESCs) and plays important roles in regulating the differentiation. Strikingly, altering Tcea3 expression in mESCs did not affect self‐renewal under nondifferentiating condition; however, upon exposure to differentiating cues, its overexpression impaired in vitro differentiation capacity, and its knockdown biased differentiation toward mesodermal and endodermal fates. Furthermore, we identified Lefty1 as a downstream target of Tcea3 and showed that the Tcea3 ‐ Lefty1 ‐Nodal‐Smad2 pathway is an innate program critically regulating cell fate choices between self‐replication and differentiation commitment. Together, we propose that Tcea3 critically regulates pluripotent differentiation of mESCs as a molecular rheostat of Nodal‐Smad2/3 signaling. S TEM C ELLS 2013;31:282–292