Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells

Summary: Human induced pluripotent stem cells (hiPSCs) show variable differentiation potential due to their epigenomic heterogeneity, whose extent/attributes remain unclear, except for well-studied elements/chromosomes such as imprints and the X chromosomes. Here, we show that seven hiPSC lines with...

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Autores principales:	Shihori Yokobayashi, Yukihiro Yabuta, Masato Nakagawa, Keisuke Okita, Bo Hu, Yusuke Murase, Tomonori Nakamura, Guillaume Bourque, Jacek Majewski, Takuya Yamamoto, Mitinori Saitou
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	human induced pluripotent stem cells clonal heterogeneity epigenome histone modifications DNA methylation X chromosome inactivation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ede168a2bf544c0b9ef86da849b5f0a5
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spelling	oai:doaj.org-article:ede168a2bf544c0b9ef86da849b5f0a52021-11-04T04:28:54ZInherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells2211-124710.1016/j.celrep.2021.109909https://doaj.org/article/ede168a2bf544c0b9ef86da849b5f0a52021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013826https://doaj.org/toc/2211-1247Summary: Human induced pluripotent stem cells (hiPSCs) show variable differentiation potential due to their epigenomic heterogeneity, whose extent/attributes remain unclear, except for well-studied elements/chromosomes such as imprints and the X chromosomes. Here, we show that seven hiPSC lines with variable germline potential exhibit substantial epigenomic heterogeneity, despite their uniform transcriptomes. Nearly a quarter of autosomal regions bear potentially differential chromatin modifications, with promoters/CpG islands for H3K27me3/H2AK119ub1 and evolutionarily young retrotransposons for H3K4me3. We identify 145 large autosomal blocks (≥100 kb) with differential H3K9me3 enrichment, many of which are lamina-associated domains (LADs) in somatic but not in embryonic stem cells. A majority of these epigenomic heterogeneities are independent of genetic variations. We identify an X chromosome state with chromosome-wide H3K9me3 that stably prevents X chromosome erosion. Importantly, the germline potential of female hiPSCs correlates with X chromosome inactivation. We propose that inherent genomic properties, including CpG density, transposons, and LADs, engender epigenomic heterogeneity in hiPSCs.Shihori YokobayashiYukihiro YabutaMasato NakagawaKeisuke OkitaBo HuYusuke MuraseTomonori NakamuraGuillaume BourqueJacek MajewskiTakuya YamamotoMitinori SaitouElsevierarticlehuman induced pluripotent stem cellsclonal heterogeneityepigenomehistone modificationsDNA methylationX chromosome inactivationBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109909- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human induced pluripotent stem cells clonal heterogeneity epigenome histone modifications DNA methylation X chromosome inactivation Biology (General) QH301-705.5
spellingShingle	human induced pluripotent stem cells clonal heterogeneity epigenome histone modifications DNA methylation X chromosome inactivation Biology (General) QH301-705.5 Shihori Yokobayashi Yukihiro Yabuta Masato Nakagawa Keisuke Okita Bo Hu Yusuke Murase Tomonori Nakamura Guillaume Bourque Jacek Majewski Takuya Yamamoto Mitinori Saitou Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
description	Summary: Human induced pluripotent stem cells (hiPSCs) show variable differentiation potential due to their epigenomic heterogeneity, whose extent/attributes remain unclear, except for well-studied elements/chromosomes such as imprints and the X chromosomes. Here, we show that seven hiPSC lines with variable germline potential exhibit substantial epigenomic heterogeneity, despite their uniform transcriptomes. Nearly a quarter of autosomal regions bear potentially differential chromatin modifications, with promoters/CpG islands for H3K27me3/H2AK119ub1 and evolutionarily young retrotransposons for H3K4me3. We identify 145 large autosomal blocks (≥100 kb) with differential H3K9me3 enrichment, many of which are lamina-associated domains (LADs) in somatic but not in embryonic stem cells. A majority of these epigenomic heterogeneities are independent of genetic variations. We identify an X chromosome state with chromosome-wide H3K9me3 that stably prevents X chromosome erosion. Importantly, the germline potential of female hiPSCs correlates with X chromosome inactivation. We propose that inherent genomic properties, including CpG density, transposons, and LADs, engender epigenomic heterogeneity in hiPSCs.
format	article
author	Shihori Yokobayashi Yukihiro Yabuta Masato Nakagawa Keisuke Okita Bo Hu Yusuke Murase Tomonori Nakamura Guillaume Bourque Jacek Majewski Takuya Yamamoto Mitinori Saitou
author_facet	Shihori Yokobayashi Yukihiro Yabuta Masato Nakagawa Keisuke Okita Bo Hu Yusuke Murase Tomonori Nakamura Guillaume Bourque Jacek Majewski Takuya Yamamoto Mitinori Saitou
author_sort	Shihori Yokobayashi
title	Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
title_short	Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
title_full	Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
title_fullStr	Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
title_full_unstemmed	Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
title_sort	inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ede168a2bf544c0b9ef86da849b5f0a5
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_version_	1718445306512670720

Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells

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