{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE322nnn/GSE322198/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE322198"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Female iPSC X-chromosome inactivation (XCI) erosion and its transcriptomic effects during CRISPR gene editing and neural differentiation","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.","dates":{"publication":"2026/03/04"},"accession":"GSE322198","cross_references":{"GSM":["GSM9551689","GSM9551568","GSM9551569","GSM9551687","GSM9551566","GSM9551688","GSM9551564","GSM9551685","GSM9551686","GSM9551565","GSM9551683","GSM9551562","GSM9551684","GSM9551563","GSM9551681","GSM9551560","GSM9551561","GSM9551682","GSM9551680","GSM9551559","GSM9551678","GSM9551557","GSM9551558","GSM9551679","GSM9551555","GSM9551676","GSM9551677","GSM9551556","GSM9551674","GSM9551553","GSM9551675","GSM9551554","GSM9551672","GSM9551551","GSM9551552","GSM9551673","GSM9551670","GSM9551671","GSM9551550","GSM9551669","GSM9551548","GSM9551549","GSM9551667","GSM9551546","GSM9551668","GSM9551547","GSM9551665","GSM9551666","GSM9551663","GSM9551664","GSM9551661","GSM9551662","GSM9551660","GSM9551658","GSM9551659","GSM9551656","GSM9551657","GSM9551654","GSM9551655","GSM9551652","GSM9551773","GSM9551774","GSM9551653","GSM9551771","GSM9551650","GSM9551772","GSM9551651","GSM9551770","GSM9551649","GSM9551647","GSM9551768","GSM9551769","GSM9551648","GSM9551766","GSM9551645","GSM9551767","GSM9551646","GSM9551764","GSM9551643","GSM9551644","GSM9551765","GSM9551641","GSM9551762","GSM9551763","GSM9551642","GSM9551760","GSM9551761","GSM9551640","GSM9551638","GSM9551759","GSM9551639","GSM9551757","GSM9551636","GSM9551758","GSM9551637","GSM9551755","GSM9551634","GSM9551635","GSM9551756","GSM9551632","GSM9551753","GSM9551754","GSM9551633","GSM9551751","GSM9551630","GSM9551752","GSM9551631","GSM9551750","GSM9551629","GSM9551748","GSM9551627","GSM9551749","GSM9551628","GSM9551746","GSM9551625","GSM9551747","GSM9551626","GSM9551744","GSM9551623","GSM9551624","GSM9551745","GSM9551621","GSM9551742","GSM9551743","GSM9551622","GSM9551740","GSM9551741","GSM9551620","GSM9551618","GSM9551739","GSM9551619","GSM9551737","GSM9551616","GSM9551738","GSM9551617","GSM9551735","GSM9551614","GSM9551615","GSM9551736","GSM9551612","GSM9551733","GSM9551734","GSM9551613","GSM9551731","GSM9551610","GSM9551732","GSM9551611","GSM9551730","GSM9551609","GSM9551728","GSM9551607","GSM9551729","GSM9551608","GSM9551726","GSM9551605","GSM9551727","GSM9551606","GSM9551724","GSM9551603","GSM9551604","GSM9551725","GSM9551601","GSM9551722","GSM9551723","GSM9551602","GSM9551720","GSM9551721","GSM9551600","GSM9551719","GSM9551717","GSM9551718","GSM9551715","GSM9551716","GSM9551713","GSM9551714","GSM9551711","GSM9551712","GSM9551710","GSM9551708","GSM9551709","GSM9551706","GSM9551707","GSM9551704","GSM9551705","GSM9551702","GSM9551703","GSM9551700","GSM9551701","GSM9551599","GSM9551597","GSM9551598","GSM9551595","GSM9551596","GSM9551593","GSM9551594","GSM9551591","GSM9551592","GSM9551590","GSM9551588","GSM9551589","GSM9551586","GSM9551587","GSM9551584","GSM9551585","GSM9551582","GSM9551583","GSM9551580","GSM9551581","GSM9551579","GSM9551698","GSM9551577","GSM9551578","GSM9551699","GSM9551575","GSM9551696","GSM9551697","GSM9551576","GSM9551694","GSM9551573","GSM9551695","GSM9551574","GSM9551692","GSM9551571","GSM9551572","GSM9551693","GSM9551690","GSM9551691","GSM9551570"],"GPL":["34281"],"GSE":["322198"],"taxon":["Homo sapiens"],"PMID":["[41890091]"]}}