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

Autor:	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
Předmět:	DENATURATION of proteins ENDOPLASMIC reticulum ISLANDS of Langerhans EIGENFUNCTIONS
Zdroj:	Cells (2073-4409); Dec2021, Vol. 10 Issue 12, p3585-3585, 1p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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