{"id":"doi:10.1038/s41556-023-01150-8","kind":"article","title":"Single-nucleus multi-omics of human stem cell-derived islets identifies deficiencies in lineage specification","authors":["Augsornworawat P","Hogrebe NJ","Ishahak M","Schmidt MD","Marquez E","Maestas MM","Veronese-Paniagua DA","Gale SE","Miller JR","Velazco-Cruz L","Millman JR"],"author_count":11,"year":2023,"published":"2023-05-15","venue":"Nature cell biology","cited_by":83,"doi":"10.1038/s41556-023-01150-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41556-023-01150-8","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41556-023-01150-8","updated":null,"pmid":"37188763","pmcid":"PMC10264244","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC10264244/pdf","abstract":"Insulin-producing β cells created from human pluripotent stem cells have potential as a therapy for insulin-dependent diabetes, but human pluripotent stem cell-derived islets (SC-islets) still differ from their in vivo counterparts. To better understand the state of cell types within SC-islets and identify lineage specification deficiencies, we used single-nucleus multi-omic sequencing to analyse chromatin accessibility and transcriptional profiles of SC-islets and primary human islets. Here we provide an analysis that enabled the derivation of gene lists and activity for identifying each SC-islet cell type compared with primary islets. Within SC-islets, we found that the difference between β cells and awry enterochromaffin-like cells is a gradient of cell states rather than a stark difference in identity. Furthermore, transplantation of SC-islets in vivo improved cellular identities overtime, while long-term in vitro culture did not. Collectively, our results highlight the importance of chromatin and transcriptional landscapes during islet cell specification and maturation.","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 \"Single-nucleus multi-omics of human stem cell-derived islets identifies deficiencies in lineage specification\" by Augsornworawat P, Hogrebe NJ, Ishahak M et al., https://doi.org/10.1038/s41556-023-01150-8, 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":[]}