Teo, A.K.K., Lim, C.S., Cheow, L.F. et al. Single-cell analyses of human islet cells reveal de-differentiation signatures. Cell Death Discovery 4, 14 (2018). https://doi.org/10.1038/s41420-017-0014-5
Human pancreatic islets containing insulin-secreting β-cells are notoriously heterogeneous in cell composition. Since β-cell failure is the root cause of diabetes, understanding this heterogeneity is of paramount importance. Recent reports have cataloged human islet transcriptome but not compared single β-cells in detail. Here, we scrutinized ex vivo human islet cells from healthy donors and show that they exhibit de-differentiation signatures. Using single-cell gene expression and immunostaining analyses, we found healthy islet cells to contain polyhormonal transcripts, and INS+ cells to express decreased levels of β-cell genes but high levels of progenitor markers. Rare cells that are doubly positive for progenitor markers/exocrine signatures, and endocrine/exocrine hormones were also present. We conclude that ex vivo human islet cells are plastic and can possibly de-/trans-differentiate across pancreatic cell fates, partly accounting for β-cell functional decline once isolated. Therefore, stabilizing β-cell identity upon isolation may improve its functionality.
A.K.K.T. is supported by the Institute of Molecular and Cell Biology (IMCB), A*STAR, NHG-KTPH SIG/14033, the NUHS-CG Metabolic In-Vitro Core Seed Funding, the JCO Career Development Award (CDA) 15302FG148, A*STAR, and the NMRC Open Fund-Young Individual Research Grant (OF-YIRG). We thank
AMPL for their histoservices. Sponsors had no involvement in the conduct of the research and/or preparation of the article.