Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cells, Vol 10, Iss 12, p 3585 (2021)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells10123585
Popis: 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.
Databáze: Directory of Open Access Journals
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