H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells

• DOI: 10.1016/j.stemcr.2016.04.015
• Publication Date: 2016-05-28T03:05:07Z
• Authors: Akira Kunitomi; Shinsuke Yuasa; Fumihiro Sugiyama; Yuki Saito; Tomohisa Seki; Dai Kusumoto; Shin Kashimura; Makoto Takei; Shugo Tohyama; Hisayuki Hashimoto; Toru Egashira; Yoko Tanimoto; Saori Mizuno; Shoma Tanaka; Hironobu Okuno; Kazuki Yamazawa; Hideo Watanabe; Mayumi Oda; Ruri Kaneda; Yumi Matsuzaki; Toshihiro Nagai; Hideyuki Okano; Ken-ichi Yagami; Mamoru Tanaka; Keiichi Fukuda
• Keywords: 0301 basic medicine; Medicine (General); QH301-705.5; Induced Pluripotent Stem Cells; Kruppel-Like Transcription Factors; Gene Expression; Mice, Transgenic; Chimerism; Epigenesis, Genetic; Histones; Proto-Oncogene Proteins c-myc; Kruppel-Like Factor 4; Mice; 03 medical and health sciences; R5-920; Report; Animals; Biology (General); 0303 health sciences; SOXB1 Transcription Factors; Fibroblasts; Cellular Reprogramming; Embryo, Mammalian; Oocytes; Female; Octamer Transcription Factor-3

Embryonic stem cells (ESCs) are a hallmark of ideal pluripotent stem cells. Epigenetic reprogramming of induced pluripotent stem cells (iPSCs) has not been fully accomplished. iPSC generation is similar to somatic cell nuclear transfer (SCNT) in oocytes, and this procedure can be used to generate ESCs (SCNT-ESCs), which suggests the contribution of oocyte-specific constituents. Here, we show that the mammalian oocyte-specific linker histone H1foo has beneficial effects on iPSC generation. Induction of H1foo with Oct4, Sox2, and Klf4 significantly enhanced the efficiency of iPSC generation. H1foo promoted in vitro differentiation characteristics with low heterogeneity in iPSCs. H1foo enhanced the generation of germline-competent chimeric mice from iPSCs in a manner similar to that for ESCs. These findings indicate that H1foo contributes to the generation of higher-quality iPSCs.