NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression

Panagiotis Mistriotis; Vivek K. Bajpai; Xiaoyan Wang; Na Rong; Aref Shahini; Mohammadnabi Asmani; Mao Shih Liang; Jianmin Wang; Pedro Lei; Song Liu; Ruogang Zhao; Stelios T. Andreadis

doi:10.1002/stem.2452

NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression

Panagiotis Mistriotis
, Vivek K. Bajpai
, Xiaoyan Wang
, Na Rong
, Aref Shahini
, Mohammadnabi Asmani
, Mao Shih Liang
, Jianmin Wang
, Pedro Lei
, Song Liu
, Ruogang Zhao
, Stelios T. Andreadis

SUNY Buffalo
Roswell Park Cancer Institute

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

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. Stem Cells 2017;35:207–221.

Original language	English
Pages (from-to)	207-221
Number of pages	15
Journal	Stem Cells
Volume	35
Issue number	1
DOIs	https://doi.org/10.1002/stem.2452
State	Published - Jan 1 2017

Keywords

ACTIN polymerization
Aging
Contraction
NANOG
Progeria
SRF
Senescence
Smooth muscle differentiation
Stem cells

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10.1002/stem.2452

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Mistriotis, P., Bajpai, V. K., Wang, X., Rong, N., Shahini, A., Asmani, M., Liang, M. S., Wang, J., Lei, P., Liu, S., Zhao, R., & Andreadis, S. T. (2017). NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression. Stem Cells, 35(1), 207-221. https://doi.org/10.1002/stem.2452

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title = "NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression",

abstract = "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{\textemdash}both of which were impaired in senescent cells{\textemdash}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. Stem Cells 2017;35:207{\textendash}221.",

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author = "Panagiotis Mistriotis and Bajpai, \{Vivek K.\} and Xiaoyan Wang and Na Rong and Aref Shahini and Mohammadnabi Asmani and Liang, \{Mao Shih\} and Jianmin Wang and Pedro Lei and Song Liu and Ruogang Zhao and Andreadis, \{Stelios T.\}",

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AU - Wang, Xiaoyan

AU - Rong, Na

AU - Shahini, Aref

AU - Asmani, Mohammadnabi

AU - Liang, Mao Shih

AU - Wang, Jianmin

AU - Lei, Pedro

AU - Liu, Song

AU - Zhao, Ruogang

AU - Andreadis, Stelios T.

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AB - 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. Stem Cells 2017;35:207–221.

KW - ACTIN polymerization

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KW - Contraction

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KW - Smooth muscle differentiation

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NANOG Reverses the Myogenic Differentiation Potential of Senescent Stem Cells by Restoring ACTIN Filamentous Organization and SRF-Dependent Gene Expression

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