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其表达受 miR-135a 调控,并在小鼠细胞重编程过程中参与 DNA 损伤修复。

is regulated by miR-135a and involved in DNA damage repair during mouse cellular reprogramming.

机构信息

Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China.

Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong Shenzhen Hospital, Shenzhen, China.

出版信息

Aging (Albany NY). 2020 Apr 26;12(8):7431-7447. doi: 10.18632/aging.103090.

Abstract

facilitates the reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs). It is regulated by micro-RNA and reported to be a target of miR-135a. However, their relationship and roles on cellular reprogramming remain unknown. In this study, we found negative correlations between miR-135a and during mouse embryonic stem cells differentiation and mouse embryonic fibroblasts reprogramming. We further found that the reprogramming efficiency was reduced by the overexpression of miR-135a precursor but induced by the miR-135a inhibitor. Co-immunoprecipitation followed by mass spectrometry identified 21 SIRT1 interacting proteins including KU70 and WRN, which were highly enriched for DNA damage repair. In accordance, activator resveratrol reduced DNA damage during the reprogramming process. was regulated by miR-135a and resveratrol partly rescued the impaired reprogramming efficiency induced by knockdown. This study showed , being partly regulated by miR-135a, bound proteins involved in DNA damage repair and enhanced the iPSCs production.

摘要

促进了小鼠体细胞重编程为诱导多能干细胞(iPSCs)。它受 micro-RNA 调控,被报道是 miR-135a 的靶标。然而,它们在细胞重编程中的关系和作用仍不清楚。在这项研究中,我们发现 miR-135a 与在小鼠胚胎干细胞分化和小鼠胚胎成纤维细胞重编程过程中呈负相关。我们进一步发现,miR-135a 前体的过表达降低了重编程效率,但 miR-135a 抑制剂诱导了重编程效率。免疫共沉淀结合质谱鉴定了 21 种 SIRT1 相互作用蛋白,包括 KU70 和 WRN,它们高度富集于 DNA 损伤修复。相应地,激活剂白藜芦醇在重编程过程中减少了 DNA 损伤。被 miR-135a 调控,与参与 DNA 损伤修复的蛋白结合,并增强 iPSCs 的产生。

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