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Omics · study · 2026

CRISPR Screening to Investigate Stem Cell-Derived Islets

Listed in NCBI GEO

Genetically engineering human pluripotent stem cell (hPSC)-derived islets is a promising strategy for improving transplantation for diabetes cell therapy.

Description

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.

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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.

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Life Sciences
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Sequencing 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE30593214 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title