Single-cell transcriptomics links loss of human pancreatic β-cell identity to er stress

Nathalie Groen, Floris Leenders, Ahmed Mahfouz, Amadeo Munoz-Garcia, Mauro J. Muraro, Natascha de Graaf, Ton J. Rabelink, Rob Hoeben, Alexander van Oudenaarden, Arnaud Zaldumbide, Marcel J.T. Reinders, Eelco J.P. de Koning, Françoise Carlotti*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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The maintenance of pancreatic islet architecture is crucial for proper β-cell function. We previously reported that disruption of human islet integrity could result in altered β-cell identity. Here we combine β-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 β-cell maturity genes. Collectively, our findings illus-trate the close relationship between endoplasmic reticulum homeostasis and β-cell phenotype, and strengthen the concept of altered β-cell identity as a mechanism underlying the loss of functional β-cell mass.

Original languageEnglish
Article number3585
Issue number12
Publication statusPublished - Dec 2021


  • ER stress
  • Human pancreatic islets
  • Islet integrity
  • Single-cell RNAseq
  • Type 2 diabetes
  • β-cells


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