{"id":"doi:10.1038/s41467-026-75255-7","kind":"article","title":"Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets","authors":["Akgün Canan M","Cozzitorto C","Sterr M","Saber L","Setyono ESA","Dema A","Kozawa K","Wang X","Merl-Pham J","Greisle T","Burtscher I","Lickert H"],"author_count":12,"year":2026,"published":"2026-07-09","venue":"Nature communications","cited_by":3,"doi":"10.1038/s41467-026-75255-7","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-026-75255-7","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-026-75255-7","updated":null,"pmid":"42426000","pmcid":"PMC13351057","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13351057/pdf","abstract":"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 combine lineage labelling with single-cell multiomic analysis in our newly generated ARX CFP/CFP ; PAX4 mCherry/mCherry knock-in induced pluripotent stem cell reporter line. Lineage tracing, proteomic and gene regulatory network analysis and potency assays reveal 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 lead to enhanced endocrine induction and directed α/β cell fate. Studying mechanisms of endocrinogenesis and fate segregation enables the engineering of islets in vitro, and has broader implications for cell-replacement therapy, disease modelling and drug screening.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Resolving human α versus β cell fate allocation for the generation of stem cell-derived islets\" by Akgün Canan M, Cozzitorto C, Sterr M et al., https://doi.org/10.1038/s41467-026-75255-7, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"gene-cell-therapy","name":"Gene & Cell Therapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}