GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE322nnn/GSE322198/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322198GEOGSEfalseFemale iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiationHuman 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.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 sapiens[41890091]