TY - JOUR
T1 - Histone variant H2A.X deposition pattern serves as a functional epigenetic mark for distinguishing the developmental potentials of iPSCs
AU - Wu, Tao
AU - Liu, Yifei
AU - Wen, Duancheng
AU - Tseng, Zito
AU - Tahmasian, Martik
AU - Zhong, Mei
AU - Rafii, Shahin
AU - Stadtfeld, Matthias
AU - Hochedlinger, Konrad
AU - Xiao, Andrew
N1 - Funding Information:
We thank Dr. Fredrick Alt (Harvard Medical School) for providing H2A.X KO ESC, Drs. David Gilbert and Tyrone Ryba for sharing the data, Dr. Anna-Katerina Hadjantonakis and Dr. Nestor Saiz Arenales for TSC line (TS3.5-GFP). A.X. is supported by a Howard Teming Award from NCI (K99/R00 CA1311560) and Yale startup funding. T.W. is partially supported by CT Stem Cell Foundation (11SCA34).
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014
Y1 - 2014
N2 - For future application of induced pluripotent stem cell (iPSC) technology, the ability to assess the overall quality of iPSC clones will be an important issue. Here we show that the histone variant H2A.X is a functional marker that can distinguish the developmental potentials of mouse iPSC lines. We found that H2A.X is specifically targeted to and negatively regulates extraembryonic lineage gene expression in embryonic stem cells (ESCs) and prevents trophectoderm lineage differentiation. ESC-specific H2A.X deposition patterns are faithfully recapitulated in iPSCs that support the development of "all-iPS" animals via tetraploid complementation, the most stringent test available of iPSC quality. In contrast, iPSCs that fail to support all-iPS embryonic development show aberrant H2A.X deposition, upregulation of extraembryonic lineage genes, and a predisposition to extraembryonic differentiation. Thus, our work has highlighted an epigenetic mechanism for maintaining cell lineage commitment in ESCs and iPSCs that can be used to distinguish the quality of iPSC lines.
AB - For future application of induced pluripotent stem cell (iPSC) technology, the ability to assess the overall quality of iPSC clones will be an important issue. Here we show that the histone variant H2A.X is a functional marker that can distinguish the developmental potentials of mouse iPSC lines. We found that H2A.X is specifically targeted to and negatively regulates extraembryonic lineage gene expression in embryonic stem cells (ESCs) and prevents trophectoderm lineage differentiation. ESC-specific H2A.X deposition patterns are faithfully recapitulated in iPSCs that support the development of "all-iPS" animals via tetraploid complementation, the most stringent test available of iPSC quality. In contrast, iPSCs that fail to support all-iPS embryonic development show aberrant H2A.X deposition, upregulation of extraembryonic lineage genes, and a predisposition to extraembryonic differentiation. Thus, our work has highlighted an epigenetic mechanism for maintaining cell lineage commitment in ESCs and iPSCs that can be used to distinguish the quality of iPSC lines.
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U2 - 10.1016/j.stem.2014.06.004
DO - 10.1016/j.stem.2014.06.004
M3 - Article
C2 - 25192463
AN - SCOPUS:84924959050
SN - 1934-5909
VL - 15
SP - 281
EP - 294
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 3
ER -