Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence
Valproic Acid Enhances iPSC Induction From Human Bone Marrow-Derived Cells Through the Suppression of Reprogramming-Induced Senescence
复制标题
丙戊酸通过抑制重编程诱导的衰老来增强人骨髓来源细胞的 iPSC 诱导
DOI：
10.1002/jcp.25270
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发表时间：
2016-08-01
影响因子：
5.6
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Chen, Xi;Zhai, Yingying;Li, Wei
通过确定的转录因子将人类体细胞重编程为多能细胞（iPSC）是一个极其低效的过程。在重编程期间用组蛋白脱乙酰酶抑制剂丙戊酸（VPA）处理可以改善iPSC的诱导。为了研究VPA在重编程中作用的具体机制，我们在VPA存在下用携带确定因子（OCT 4、SOX 2、KLF 4和c-MYC、OSKM）的慢病毒转染人骨髓源性细胞（HSC-J2和HSC-L1）。我们发现，OSKM慢病毒在转染的细胞中引起显著的衰老。然而，VPA的管理，显着抑制这种重编程诱导的压力。值得注意的是，VPA处理改善了重编程早期阶段的细胞增殖，这与激活的p16/p21通路的下调有关。此外，VPA还可解除慢病毒转染细胞的G2/M期阻滞。本研究证明了组蛋白去乙酰化酶抑制剂在增强多能性诱导中的新机制作用。(C)2015 Wiley Periodicals，Inc.
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. (C) 2015 Wiley Periodicals, Inc.