Two Histone Variants TH2A and TH2B Enhance Human Induced Pluripotent Stem Cell Generation

Linh My Huynh, Toshie Shinagawa, Shunsuke Ishii

Research output: Contribution to journalArticlepeer-review

Abstract

There are two major methods of reprogramming: generation of induced pluripotent stem cells (iPSCs) by overexpressing embryonic stem cell-specific transcription factors (OCT4, SOX2, KLF4, and c-MYC) and somatic cell nuclear transfer by oocyte-specific factors. Previously, we reported oocyte-enriched histone variants TH2A, TH2B, and the histone chaperone nucleoplasmin (NPM2) enhance the reprogramming by OSKM in mice by inducing open chromatin structure. In this study, we showed that human TH2A, TH2B, and NPM2 enhance the OSKM-induced reprogramming of adult and neonatal human dermal fibroblasts and umbilical vein endothelial cells. Pluripotency of iPSCs generated by coexpressing OSKM, TH2A, TH2B, and NPM2 was shown by in vitro and in vivo differentiation assays. These iPSCs gave rise to highly differentiated teratomas compared to iPSCs induced by OSKM alone. Genome-wide analysis suggests a possibility that TH2A, TH2B, and NPM2 might regulate genes that are involved in naïve stem cell stage. Thus, TH2A, TH2B, and NPM2 enhance reprogramming of human somatic cells and improve the quality of human iPSCs.

Original languageEnglish
Pages (from-to)251-8
Number of pages8
JournalStem Cells and Development
Volume25
Issue number3
DOIs
Publication statusPublished - 1 Feb 2016

Keywords

  • Cellular Reprogramming
  • Fibroblasts
  • Histones
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Induced Pluripotent Stem Cells
  • Kruppel-Like Transcription Factors
  • Nucleoplasmins
  • Octamer Transcription Factor-3
  • Protein Isoforms
  • Proto-Oncogene Proteins c-myc
  • SOXB1 Transcription Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't

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