GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301598/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301598GEOGSEfalseComparative single-cell transcriptomic analysis of human primary and stem cell-derived islets under acute hypoxiaTo understand the divergent responses of different islet sources to the hypoxic stress encountered post-transplantation, we performed a direct, comparative single-cell RNA sequencing analysis of human primary islets and stem cell-derived islets (SC-islets, HUES8 line) over an acute time course (0, 6, 24, and 48 hours) of hypoxic exposure (1% O2). Our data reveal that while both islet types activate conserved core stress pathways, they subsequently execute markedly divergent adaptive strategies. Primary β-cells navigate hypoxia through a profound suppression of their mature identity and a shift towards a quiescent, energy-conserving state. In contrast, SC-β cells mount a highly plastic and metabolically dynamic response that is coupled with significant lineage instability and functional dysregulation. These findings highlight fundamental, source-specific differences in hypoxic adaptation, providing a rich resource for developing tailored strategies to improve islet transplantation success.2026/04/28GSE301598GSM908626924676301598Homo sapiens