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

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

Huynh LM1,2,3, Shinagawa T1,2,3, Ishii S1,2,3.

Author information

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 .

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.

PMID:
26649967
DOI:
10.1089/scd.2015.0264
[Indexed for MEDLINE]

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