Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence
- 28 December 2015
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 231 (8), 1719-1727
- https://doi.org/10.1002/jcp.25270
Abstract
Reprogramming of human somatic cells into pluripotent cells (iPSCs) by defined transcription factors is an extremely inefficient process. Treatment with the histone deacetylase inhibitor valproic acid (VPA) during reprogramming can improve the induction of iPSCs. To examine the specific mechanism underlying the role of VPA in reprogramming, we transfected human bone marrow-derived cells (HSC-J2 and HSC-L1) with lentiviruses carrying defined factors (OCT4, SOX2, KLF4, and c-MYC, OSKM) in the presence of VPA. We found that, OSKM lentiviruses caused significant senescence in transfected cells. Administration of VPA, however, significantly suppressed this reprogramming-induced stress. Notably, VPA treatment improved cell proliferation in the early stages of reprogramming, and this was related to the down-regulation of the activated p16/p21 pathway. In addition, VPA also released the G2/M phase blockade in lentivirus-transfected cells. This study demonstrates a new mechanistic role of the histone deacetylase inhibitor in enhancing the induction of pluripotency. J. Cell. Physiol. 231: 1719-1727, 2016. © 2015 Wiley Periodicals, Inc.Keywords
Funding Information
- California Institute of Regenerative Medicine (RT2-01942)
- Jilin International Collaboration (#20120720, 20130413010GH)
- National Natural Science Foundation of China (#81272294, #31430021, #81071920, #81372835, #81302380)
- Jilin Science and Technique Program (11GG003)
- Key Clinical Project of the Ministry of Health of the People's Republic of China (2001133)
- Key Project of Chinese Ministry of Education (311015)
- Development Foundation for Youths of Jilin Provincial Science & Technology Department (#20140520017JH)
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