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

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

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.

Keywords: Epigenetic modification; Kdm1b; Pluripotency; Proliferation; Reprogramming.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cellular Reprogramming* / genetics
  • Fibroblasts / metabolism
  • Gene Expression
  • Histones / metabolism
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Lysine / metabolism
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Oxidoreductases, N-Demethylating* / metabolism

Substances

  • Histones
  • Lysine
  • Octamer Transcription Factor-3
  • Oxidoreductases, N-Demethylating
  • KDM1B protein, human