title: Calcineurin-NFAT Signaling Controls Somatic Cell Reprogramming in a Stage-Dependent Manner.
abstract: Calcineurin-NFAT signaling is critical for early lineage specification of mouse embryonic stem cells and early embryos. However, its roles in somatic cell reprogramming remain unknown. Here, we report that calcineurin-NFAT signaling has a dynamic activity and plays diverse roles at different stages of reprogramming. At the early stage, calcineurin-NFAT signaling is transiently activated and its activation is required for successful reprogramming. However, at the late stage of reprogramming, activation of calcineurin-NFAT signaling becomes a barrier for reprogramming and its inactivation is critical for successful induction of pluripotency. Mechanistically, calcineurin-NFAT signaling contributes to the reprogramming through regulating multiple early events during reprogramming, including mesenchymal to epithelial transition (MET), cell adhesion and emergence of SSEA1(+) intermediate cells. Collectively, this study reveals for the first time the important roles of calcineurin-NFAT signaling during somatic cell reprogramming and provides new insights into the molecular regulation of reprogramming.
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.|Shanghai Stem Cell Institute, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liao
authors.affiliation: National Institute of Biological Sciences, Beijing, China.|The College of Life Science, Beijing Normal University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.|Shanghai Stem Cell Institute, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Gu
authors.affiliation: School of Life Sciences and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Tongji University, Shanghai, China.
authors.forename: Shaorong
authors.initials: S
authors.lastname: Gao
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.|Shanghai Stem Cell Institute, Shanghai JiaoTong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D065150:Cellular Reprogramming; D005786:Gene Expression Regulation; D008810:Mice, Inbred C57BL; D050778:NFATC Transcription Factors / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D050778:NFATC Transcription Factors; D019703:Calcineurin