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, 2017 01.
Article
in En
| MEDLINE
| ID: mdl-27350449
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)-ß 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;35207-221.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Cell Differentiation
/
Gene Expression Regulation
/
Actins
/
Cellular Senescence
/
Serum Response Factor
/
Mesenchymal Stem Cells
/
Nanog Homeobox Protein
Type of study:
Prognostic_studies
Limits:
Aged
/
Humans
Language:
En
Year:
2017
Type:
Article