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- Title
Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress.
- Authors
Groen, Nathalie; Leenders, Floris; Mahfouz, Ahmed; Munoz-Garcia, Amadeo; Muraro, Mauro J.; de Graaf, Natascha; Rabelink, Ton. J.; Hoeben, Rob; van Oudenaarden, Alexander; Zaldumbide, Arnaud; Reinders, Marcel J. T.; Koning, Eelco J. P. de; Carlotti, Françoise
- 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.
- Subjects
DENATURATION of proteins; ENDOPLASMIC reticulum; ISLANDS of Langerhans; EIGENFUNCTIONS
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 12, p3585
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10123585