# Single-nucleus multi-omics of human stem cell-derived islets identifies deficiencies in lineage specification

Article · Augsornworawat P, Hogrebe NJ, Ishahak M, Schmidt MD, Marquez E, Maestas MM, Veronese-Paniagua DA, Gale SE, Miller JR, Velazco-Cruz L, Millman JR

- Archive id: doi:10.1038/s41556-023-01150-8
- Published: 2023-05-15
- Venue: Nature cell biology
- DOI: https://doi.org/10.1038/s41556-023-01150-8
- PMID: 37188763
- PMCID: PMC10264244
- Citations: 83
- Source URL: https://doi.org/10.1038/s41556-023-01150-8
- PDF: https://europepmc.org/articles/PMC10264244/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Gene & Cell Therapy](https://space-kitty.com/topics/gene-cell-therapy)

Cited in dossiers:
- [Gene & Cell Therapy: State of the Field (October 2026)](https://space-kitty.com/dossiers/gene-cell-therapy)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.