Open AccessNANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF‐Dependent Gene Expression
Author(s) -
Mistriotis Panagiotis,
Bajpai Vivek K.,
Wang Xiaoyan,
Rong Na,
Shahini Aref,
Asmani Mohammadnabi,
Liang MaoShih,
Wang Jianmin,
Lei Pedro,
Liu Song,
Zhao Ruogang,
Andreadis Stelios T.
Publication year - 2017
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.2452
Subject(s) - biology , homeobox protein nanog , microbiology and biotechnology , reprogramming , induced pluripotent stem cell , stem cell , ectopic expression , cellular differentiation , serum response factor , senescence , embryonic stem cell , gene expression , genetics , cell , gene
Cellular senescence as a result of organismal aging or progeroid diseases leads to stem cell pool exhaustion hindering tissue regeneration and contributing to the progression of age related disorders. Here we discovered that ectopic expression of the pluripotent factor NANOG in senescent or progeroid myogenic progenitors reversed cellular aging and restored completely the ability to generate contractile force. To elicit its effects, NANOG enabled reactivation of the ROCK and Transforming Growth Factor (TGF)‐β pathways—both of which were impaired in senescent cells—leading to ACTIN polymerization, MRTF‐A translocation into the nucleus and serum response factor (SRF)‐dependent myogenic gene expression. Collectively our data reveal that cellular senescence can be reversed and provide a novel strategy to regain the lost function of aged stem cells without reprogramming to the pluripotent state. S tem C ells 2017;35:207–221