GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305932/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305932GEOGSEfalseCRISPR Screening to Investigate Stem Cell-Derived IsletsGenetically engineering human pluripotent stem cell (hPSC)-derived islets is a promising strategy for improving transplantation for diabetes cell therapy. However, genetic perturbations for improving transplantation efficacy have yet to be elucidated. To identify potential targets, we performed an unbiased whole-genome CRISPR-activation screen in transplanted stem cell-derived islets (SC-islets). We first created a stem cell line with CRISPR-activation components (HUES8-VPR). We transduced the HUES8-VPR stem cells with a lentiviral guide RNA library targeting the whole human genome. These transduced stem cells were differentiated into SC-islets, transplanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) immunodeficient mice, and then extracted for next-generation sequencing. The screen identified multiple candidates, including the Fc alpha/mu receptor (FCAMR). In vitro characterization revealed that FCAMR overexpression did not negatively affect SC-islet function or transcriptomic identity. Mice transplanted with SC-islets overexpressing FCAMR had increased blood glucose levels and increased cpeptide compared to controls. Furthermore, mice receiving FCAMR-modified grafts maintained a higher body weight compared to controls in a diabetic setting. Our study utilizes a screening approach to identify potential candidates for improving SC-islet therapies.2026/05/20GSE305932GSM9188175GSM918817634284305932Homo sapiens[41886504]