Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells

Mason D. Schmidt, Matthew Ishahak, Punn Augsornworawat, Jeffrey R. Millman

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetes cell replacement therapy has the potential to be transformed by human pluripotent stem cell-derived β cells (SC-β cells). However, the precise identity of SC-β cells in relationship to primary fetal and adult β-cells remains unclear. Here, we used single-cell sequencing datasets to characterize the transcriptional identity of islets from in vitro differentiation, fetal islets, and adult islets. Our analysis revealed that SC-β cells share a core β-cell transcriptional identity with human adult and fetal β-cells, however SC-β cells possess a unique transcriptional profile characterized by the persistent expression and activation of progenitor and neural-biased gene networks. These networks are present in SC-β cells, irrespective of the derivation protocol used. Notably, fetal β-cells also exhibit this neural signature at the transcriptional level. Our findings offer insights into the transcriptional identity of SC-β cells and underscore the need for further investigation of the role of neural transcriptional networks in their development.

Original languageEnglish
Article number105
JournalBMC genomics
Volume25
Issue number1
DOIs
StatePublished - Dec 2024

Keywords

  • Diabetes
  • Gene networks
  • Immaturity
  • sc-RNAseq
  • SC-β
  • Transcriptome

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