{"doi":"10.1101/2024.11.19.624394","title":"Controlling human stem cell-derived islet composition using magnetic sorting","abstract":"ABSTRACT Stem cell-derived islets (SC-islets) consists of multiple hormone-producing cell types and offer a promising therapeutic avenue for treating type 1 diabetes (T1D). Currently, the composition of cell types generated within these SC-islets currently cannot be controlled via soluble factors during this differentiation process and consist of off-target cell types. In this study, we devised a magnetic-activated cell sorting (MACS) protocol to enrich SC-islets for CD49a, a marker associated with functional insulin-producing β cells. SC-islets were generated from human pluripotent stem cells (hPSCs) using an adherent differentiation protocol and then sorted and aggregated into islet-like clusters to produce CD49a-enriched, CD49a-depleted, and unsorted SC-islets. Single-cell RNA sequencing (scRNA-seq) and immunostaining revealed that CD49a-enriched SC-islets had higher proportions of β cells and improved transcriptional identity compared to other cell types. Functional assays demonstrated that CD49a-enriched SC-islets exhibited enhanced glucose-stimulated insulin secretion both in vitro and in vivo following transplantation into diabetic mice. These findings suggest that CD49a-based sorting significantly improves β cell identity and the overall function of SC-islets, improving their effectiveness for T1D cell replacement therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":492450,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1208998,"name":"Mira Shunkarova","orcid":null,"position":1,"is_corresponding":false},{"id":565804,"name":"Marlie M. Maestas","orcid":"0000-0003-4396-9770","position":2,"is_corresponding":false},{"id":469142,"name":"Sarah E. Gale","orcid":"0000-0001-8762-4497","position":3,"is_corresponding":false},{"id":250008,"name":"Nathaniel J. Hogrebe","orcid":"0000-0002-6282-2056","position":4,"is_corresponding":false},{"id":7381,"name":"Jeffrey R. Millman","orcid":"0000-0003-0426-3492","position":5,"is_corresponding":false},{"id":1339155,"name":"Allison B. Kelley","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:08:56.210382Z","pmid":"39605713","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}