H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells

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

doi:10.1016/j.stemcr.2016.04.015

H1foo Has a Pivotal Role in Qualifying Induced Pluripotent Stem Cells

Stem Cell Reports. 2016 Jun 14;6(6):825-833. doi: 10.1016/j.stemcr.2016.04.015. Epub 2016 May 26.

Authors

Akira Kunitomi¹, Shinsuke Yuasa², Fumihiro Sugiyama³, Yuki Saito¹, Tomohisa Seki¹, Dai Kusumoto¹, Shin Kashimura¹, Makoto Takei¹, Shugo Tohyama¹, Hisayuki Hashimoto¹, Toru Egashira¹, Yoko Tanimoto³, Saori Mizuno³, Shoma Tanaka⁴, Hironobu Okuno⁴, Kazuki Yamazawa⁵, Hideo Watanabe⁶, Mayumi Oda⁷, Ruri Kaneda¹, Yumi Matsuzaki⁴, Toshihiro Nagai⁸, Hideyuki Okano⁴, Ken-Ichi Yagami³, Mamoru Tanaka⁹, Keiichi Fukuda¹

Affiliations

¹ Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
² Department of Cardiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address: yuasa@keio.jp.
³ Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
⁴ Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.
⁵ Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan.
⁶ Division of Pulmonary, Critical Care and Sleep Medicine, Departments of Medicine and Genetics and Genomic Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
⁷ Sakaguchi Laboratory, Department of Systems Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan.
⁸ Electron Microscope Laboratory, Keio University School of Medicine, Tokyo 160-8582, Japan.
⁹ Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan.

Abstract

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.

MeSH terms

Animals
Cellular Reprogramming*
Chimerism
Embryo, Mammalian
Epigenesis, Genetic*
Female
Fibroblasts / cytology
Fibroblasts / metabolism
Gene Expression
Histones / genetics*
Histones / metabolism
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / metabolism*
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism
Mice
Mice, Transgenic
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism
Oocytes / cytology
Oocytes / metabolism*
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism
SOXB1 Transcription Factors / genetics
SOXB1 Transcription Factors / metabolism

Substances

H1f8 protein, mouse
Histones
Klf4 protein, mouse
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors
Myc protein, mouse
Octamer Transcription Factor-3
Pou5f1 protein, mouse
Proto-Oncogene Proteins c-myc
SOXB1 Transcription Factors
Sox2 protein, mouse