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

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

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 illustrate 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
JournalCells
Volume10
Issue number12
DOIs
Publication statusPublished - 19 Dec 2021

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