Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells
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固有的基因组特性是人类诱导多能干细胞表观基因组异质性的基础
DOI：
10.1016/j.celrep.2021.109909
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发表时间：
2021
期刊：
影响因子：
8.8
通讯作者：
Saitou Mitinori
中科院分区：
文献类型：
--
作者：
Yokobayashi Shihori;Yabuta Yukihiro;Nakagawa Masato;Okita Keisuke;Hu Bo;Murase Yusuke;Nakamura Tomonori;Bourque Guillaume;Majewski Jacek;Yamamoto Takuya;Saitou Mitinori
人类诱导多能干细胞（hiPSC）由于其表观基因组异质性而显示可变的分化潜力，其程度/属性仍不清楚，除了充分研究的元件/染色体如印记和X染色体。在这里，我们表明，7个hiPSC线与可变的种系潜力表现出显着的表观基因组异质性，尽管他们的统一的转录组。近四分之一的常染色体区域具有潜在的差异染色质修饰，H3 K27 me 3/H2 AK 119 ub 1具有启动子/CpG岛，H3 K4 me 3具有进化上年轻的反转录转座子。我们鉴定了145个具有差异H3 K9 me 3富集的大常染色体块（≥100 kb），其中许多是体细胞中的核纤层相关结构域（LAD），而不是胚胎干细胞中的核纤层相关结构域。这些表观基因组异质性中的大多数与遗传变异无关。我们确定了一个X染色体状态与染色体范围的H3 K9 me 3，稳定地防止X染色体侵蚀。重要的是，雌性hiPSC的生殖系潜力与X染色体失活相关。我们提出，固有的基因组特性，包括CpG密度，转座子，和LAD，在hiPSC中产生表观基因组异质性。
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.