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

Linh My Huynh; Toshie Shinagawa; Shunsuke Ishii

doi:10.1089/scd.2015.0264

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

Stem Cells Dev. 2016 Feb 1;25(3):251-8. doi: 10.1089/scd.2015.0264. Epub 2016 Jan 7.

Authors

Linh My Huynh^{1

2

3}, Toshie Shinagawa^{1

2

3}, Shunsuke Ishii^{1

2

3}

Affiliations

¹ 1 Laboratory of Molecular Genetics, RIKEN Tsukuba Institute , Tsukuba, Japan .
² 2 CREST Research Project of JST (Japan Science and Technology Agency) , Tsukuba, Japan .
³ 3 Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba , Tsukuba, Japan .

PMID: 26649967
DOI: 10.1089/scd.2015.0264

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cellular Reprogramming*
Fibroblasts / cytology
Fibroblasts / metabolism
Histones / genetics
Histones / metabolism*
Human Umbilical Vein Endothelial Cells / cytology
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
Nucleoplasmins / genetics
Nucleoplasmins / metabolism
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism
Protein Isoforms / genetics
Protein Isoforms / metabolism
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism

Substances

Histones
KLF4 protein, human
Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
NPM2 protein, human
Nucleoplasmins
Octamer Transcription Factor-3
POU5F1 protein, human
Protein Isoforms
Proto-Oncogene Proteins c-myc
SOX2 protein, human
SOXB1 Transcription Factors