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Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (RNA-Seq)

ABSTRACT: Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (RNA-Seq)

PROVIDER: PRJNA1090871 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28421223_1.fastq.gz	Fastqsanger.gz
	SRR28421223_2.fastq.gz	Fastqsanger.gz
	SRR28421224_1.fastq.gz	Fastqsanger.gz
	SRR28421224_2.fastq.gz	Fastqsanger.gz
	SRR28421225_1.fastq.gz	Fastqsanger.gz

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Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (Bisulfite-seq)

Project description:During culture, female human pluripotent stem cells (hPSCs), including human induced PSCs (hiPSCs) exhibit a propensity for erosion of X-chromosome inactivation (XCI). This phenomenon is characterized by loss of XIST RNA expression and reactivation of a subset of X-linked genes from the inactive X chromosome (Xi). XCI erosion, despite its common occurrence, is often overlooked by the stem cell community, hindering a complete understanding of its impact on both fundamental and translational applications of hiPSCs. Investigating erosion dynamics in female hiPSCs, our study reveals that XCI erosion is a frequent yet heterogeneous phenomenon, resulting in reactivation of several X-linked genes. The likelihood of a gene to erode increases for those located on the short arm of the X chromosome and within H3K27me3-enriched domains. Paradoxically, genes that typically escape XCI are hypersensitive to loss of XIST RNA and XCI erosion. This implies that XIST RNA normally restrain expression levels of these genes on the Xi. Importantly, increased X-linked gene expression upon erosion does not globally impact (hydroxy)methylation levels in hiPSCs or at imprinted regions. By exploring diverse differentiation paradigms, such as trilineage commitment and cardiac differentiation, our study reveals the persistence of abnormal XCI patterns throughout differentiation. This finding has significant implications for fundamental research, translational applications, and clinical use of stem cells. We underscore the importance of raising awareness within the stem cell community regarding XCI erosion and advocate for its inclusion in comprehensive hiPSC quality control.

2025-05-13 | GSE262236 | GEO

Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (RNA-Seq)

Project description:During culture, female human pluripotent stem cells (hPSCs), including human induced pluripotent stem cells (hiPSCs), exhibit a propensity for erosion of X-chromosome inactivation (XCI). This phenomenon is characterized by the loss of XIST RNA expression and reactivation of a subset of X-linked genes from the inactive X chromosome (Xi). Despite its common occurrence, XCI erosion is often overlooked by the stem cell community, hindering a complete understanding of its impact on both fundamental and translational applications of hiPSCs. Our study investigates erosion dynamics in female hiPSCs and reveals that XCI erosion is a frequent yet heterogeneous phenomenon, resulting in the reactivation of several X-linked genes. The likelihood of a gene to erode increases for those located on the short arm of the X chromosome and within H3K27me3-enriched domains. Paradoxically, genes that typically escape XCI are hypersensitive to the loss of XIST RNA and XCI erosion. This implies that XIST RNA normally restrains expression levels of these genes on the Xi. Importantly, increased X-linked gene expression upon erosion does not globally impact (hydroxy)methylation levels in hiPSCs or at imprinted regions. By exploring diverse differentiation paradigms, such as trilineage commitment and cardiac differentiation, our study reveals the persistence of abnormal XCI patterns throughout differentiation. This finding has significant implications for fundamental research, translational applications, and clinical use of stem cells. We underscore the importance of raising awareness within the stem cell community regarding XCI erosion and advocate for its inclusion in comprehensive hiPSC quality control.

2025-05-13 | GSE262233 | GEO

Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (RNA-AMP-Seq)

2025-05-13 | GSE262238 | GEO

Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (Bisulfite-seq)

Project description:Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (Bisulfite-seq)

| PRJNA1090872 | ENA

Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (RNA-AMP-Seq)

Project description:Erosion of X-Chromosome Inactivation in female hiPSCs is heterogeneous and persists during differentiation (RNA-AMP-Seq)

| PRJNA1090873 | ENA

Gene reactivation upon erosion of X-chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation

Project description:Female human induced pluripotent stem cells frequently undergo X-chromosome inactivation (XCI) erosion, marked by XIST RNA loss and partial reactivation of the inactive X (Xi). This overlooked phenomenon limits our understanding of its impact on stem cell applications. Here, we show that XCI erosion is frequent and heterogeneous, leading to the reactivation of several X-linked genes. These are primarily located on the short arm of the X chromosome, particularly near escape genes and within H3K27me3-enriched domains, with reactivation linked to reduced promoter DNA methylation. Interestingly, escape genes further increase their expression from Xi upon XCI erosion, highlighting the critical role of XIST in their dosage regulation. Importantly, global (hydroxy)methylation levels and imprinted regions remain unaffected, and analysis of trilineage commitment and cardiomyocyte formation reveals that XCI erosion persists across differentiation. These findings underscore the need for greater awareness of the implications of XCI erosion for stem cell research and clinical applications.

2025-05-13 | GSE262239 | GEO

Gene reactivation upon erosion of X-chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation

Project description:Gene reactivation upon erosion of X-chromosome inactivation in female hiPSCs is predictable yet variable and persists through differentiation

| PRJNA1090865 | ENA

Project description:Erosion of X-Chromosome Inactivation in female hiPSCs

| PRJNA1090542 | ENA

Female iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation

Project description:Human induced pluripotent stem cells (hiPSC) and iPSC-differentiated neural cells, in combination with CRISPR editing, are commonly used for studying neurodevelopmental and other brain disorders. Female iPSCs undergo random X-chromosome inactivation (XCI) via epigenetic silencing by noncoding X inactive specific transcript (XIST). It is known that female iPSCs may lose XIST expression, leading to XCI erosion that affects both X-linked and autosomal gene expression. However, the effects of CRSIPR editing and neural differentiation on XCI erosion in iPSC-derived neurons and how this may confound a real-world transcriptomic analysis of differentially expressed genes (DEGs) are poorly understood. Here, leveraging bulk RNA-seq of hundreds of CRISPR-edited female iPSC lines from four donor lines for 66 genes and single-cell RNA-seq of iPSC-derived neurons of a subset of 42 edited genes, we investigated the effects of XCI erosion during CRISPR editing and in iPSC-derived neurons. We found that XCI erosion was variable in CRISPR-edited female iPSCs and largely preserved in iPSC-derived neurons. Like in iPSCs, XIST in neurons predominately influenced the expression of X-linked genes; however, its effect on autosomal genes was more pronounced in single neurons. Mechanistically, XIST epigenetically causes allelic imbalance of both X-linked and autosomal genes, with the former showing stronger allele-specific expression (ASE) bias. Notably, XIST-induced ASE bias exhibited a conserved positional pattern at loci affecting neurodevelopmental genes across different female lines and cell types. Finally, we demonstrated a confounding effect of XCI erosion on DEG analyses in iPSC-derived neurons. These results have significant implications in hiPSC modeling of neurodevelopmental and other brain disorders.

2026-03-04 | GSE322198 | GEO

Comparison of saliva from healthy and patients with dental erosion

Project description:To compare the salivary proteins from healthy and dental erosion patients to determine if there is an absence of proteins forming the enamel pellicle that may reduce their protection from acid erosion

2023-05-10 | PXD035565 | Pride

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