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Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells [RNA-seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165868 | GEO | 2021/11/03

REPOSITORIES: GEO

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Inherent genomic properties underlie the epigenomic heterogeneity of human induced pluripotent stem cells [ChIP-seq]

Project description: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.

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