Single-cell transcriptomics links loss of human pancreatic beta-cell identity to ER stress

Groen, N.; Leenders, F.; Mahfouz, A.; Munoz-Garcia, A.; Muraro, M.J.; Graaf, N. de; ... ; Carlotti, F. (2021)

Article / Letter to editor

The maintenance of pancreatic islet architecture is crucial for proper beta-cell function. We previously reported that disruption of human islet integrity could result in altered beta-cell identity. Here we combine beta-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of beta-cell maturity genes. Collectively, our findings illustrate the close relationship between endoplasmic reticulum homeostasis and beta-cell phenotype, and strengthen the concept of altered beta-cell identity as a mechanism underlying the loss of functional beta-cell mass.

• human pancreatic islets
• beta-cells
• ER stress
• islet integrity
• single-cell RNAseq
• type 2 diabetes

• All authors: Groen, N.; Leenders, F.; Mahfouz, A.; Munoz-Garcia, A.; Muraro, M.J.; Graaf, N. de; Rabelink, T.J.; Hoeben, R.; Oudenaarden, A. van; Zaldumbide, A.; Reinders, M.J.T.; Koning, E.J.P.D.; Carlotti, F.
• Date: 2021-12-01
• Journal: Cells
• Volume: 10
• Issue: 12
• DOI: doi:10.3390/cells10123585
• Link: https://www.mdpi.com/2073-4409/10/12/3585/pdf