赖氨酸去甲基化酶 1B（Kdm1b）通过诱导多能基因表达和促进细胞增殖来增强体细胞重编程。

Lysine demethylase 1B (Kdm1b) enhances somatic reprogramming through inducing pluripotent gene expression and promoting cell proliferation.

机构信息

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, PR China; College of Chemistry, Jilin University, Changchun, Jilin, 130021, PR China.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, PR China.

出版信息

Exp Cell Res. 2022 Nov 1;420(1):113339. doi: 10.1016/j.yexcr.2022.113339. Epub 2022 Sep 6.

DOI:10.1016/j.yexcr.2022.113339

PMID:36075448

Abstract

Lysine demethylase 1B (Kdm1b) is known as an epigenetic modifier with demethylase activity against H3K4 and H3K9 histones and plays an important role in tumor progression and tumor stem cell enrichment. In this study, we attempted to elucidate the role of Kdm1b in somatic cell reprogramming. We found that exogenous expression of Kdm1b in human dermal fibroblasts (HDFs) can influence the epigenetic modifications of histones. Subsequent analysis further suggests that the overexpression of Kdm1b can promote cell proliferation, reprogram metabolism and inhibit cell apoptosis. In addition, a series of multipotent factors including Sox2 and Nanog, and several epigenetic factors that may reduce epigenetic barriers were upregulated to varying degrees. More importantly, HDFs transfected with the combination of Oct4 (POU5F1), Sox2, Klf4 and c-Myc and Kdm1b (OSKMK) achieved higher reprogramming efficiency. Therefore, we suggest that Kdm1b is an important epigenetic factor associated with pluripotency.

摘要

赖氨酸去甲基化酶 1B（Kdm1b）是一种具有组蛋白 H3K4 和 H3K9 去甲基化酶活性的表观遗传修饰物，在肿瘤进展和肿瘤干细胞富集中发挥重要作用。在这项研究中，我们试图阐明 Kdm1b 在体细胞核重编程中的作用。我们发现，外源表达 Kdm1b 可以影响人真皮成纤维细胞（HDFs）中的组蛋白表观遗传修饰。进一步的分析表明，Kdm1b 的过表达可以促进细胞增殖、重编程代谢并抑制细胞凋亡。此外，一系列多能因子，包括 Sox2 和 Nanog，以及一些可能降低表观遗传障碍的表观遗传因子，都被不同程度地上调。更重要的是，转染了 Oct4（POU5F1）、Sox2、Klf4 和 c-Myc 以及 Kdm1b（OSKMK）的 HDFs 实现了更高的重编程效率。因此，我们认为 Kdm1b 是一种与多能性相关的重要表观遗传因子。