{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE264nnn/GSE264015/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Genome binding/occupancy profiling by high throughput sequencing","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE264015"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets","description":"Stem cell-derived glucagon-(α) and insulin-producing (β) cells allow to engineer in vitro biomimetics of islet of Langerhans, the micro-organ controlling glycemia; however, a knowledge gap in the mechanism by which human stem cell-derived α and β cells are specified persists. Mouse studies postulated that Aristaless Related homeobox (Arx) and Paired box 4 (Pax4) transcription factors cross-inhibit each other in endocrine progenitors to promote α/β fate allocation, respectively. To test this model in human, we combined lineage labeling with single-cell multiomic analysis in our newly generated ARXCFP/CFP; PAX4mCherry/mCherry knock-in induced pluripotent stem cell reporter line. Lineage tracing, proteomic and gene regulatory network analysis and potency assays revealed a human specific regulation of α/β cell fate allocation. Pharmacological perturbations previously proposed to trigger α-to-β transdifferentiation or identified by our gene regulatory network led to enhanced endocrine induction and directed α/β cell fate. Studying mechanisms of endocrinogenesis and fate segregation enables to engineer islets in vitro, and has broader implications for cell-replacement therapy, disease modelling and drug screening.","dates":{"publication":"2026/04/28"},"accession":"GSE264015","cross_references":{"GSM":["GSM8208834","GSM8208835","GSM8208832","GSM8208833","GSM8208830","GSM8208831","GSM8208829","GSM8208827","GSM8208828","GSM8208826"],"GPL":["24676"],"GSE":["264015"],"taxon":["Homo sapiens"]}}