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Calcineurin‐NFAT Signaling Controls Somatic Cell Reprogramming in a Stage‐Dependent Manner
Author(s) -
Sun Ming,
Liao Bing,
Tao Yu,
Chen Hao,
Xiao Feng,
Gu Junjie,
Gao Shaorong,
Jin Ying
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25212
Subject(s) - reprogramming , nfat , calcineurin , microbiology and biotechnology , somatic cell , biology , embryonic stem cell , cellular differentiation , signal transduction , transcription factor , stem cell , cell , genetics , transplantation , medicine , gene
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. J. Cell. Physiol. 231: 1151–1162, 2016. © 2015 Wiley Periodicals, Inc.