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-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.
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Mistriotis
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Bajpai
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Rong
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Aref
authors.initials: A
authors.lastname: Shahini
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Mohammadnabi
authors.initials: M
authors.lastname: Asmani
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Mao-Shih
authors.initials: MS
authors.lastname: Liang
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Lei
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Ruogang
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Bioengineering Laboratory, Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.|Department of Biomedical Engineering, University at Buffalo, The State University of New York, Amherst, New York, USA.
authors.forename: Stelios T
authors.initials: ST
authors.lastname: Andreadis
mesh_terms: D000199:Actins / Q000378:metabolism*; D000368:Aged; D002454:Cell Differentiation / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics; D058628:Myofibroblasts / Q000378:metabolism; D000071317:Nanog Homeobox Protein / Q000378:metabolism*; D010641:Phenotype; D011371:Progeria / Q000235:genetics / Q000473:pathology; D026362:Serum Response Factor / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000199:Actins; C431575:MRTFA protein, human; D000071317:Nanog Homeobox Protein; D026362:Serum Response Factor; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D054460:rho-Associated Kinases
keywords: ACTIN polymerization; Aging; Contraction; NANOG; Progeria; SRF; Senescence; Smooth muscle differentiation; Stem cells