BMC Genomics (Jan 2024)

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

DOI
https://doi.org/10.1186/s12864-024-10013-x
Journal volume & issue
Vol. 25, no. 1
pp. 1 – 18

Abstract

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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.

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