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Stem Cells. 2017 Jan;35(1):207-221. doi: 10.1002/stem.2452. Epub 2016 Jul 11.

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

Author information

1
Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
2
Department of Biomedical Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
3
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USA.

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.

KEYWORDS:

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

PMID:
27350449
DOI:
10.1002/stem.2452
[Indexed for MEDLINE]
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