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Cells ; 10(12)2021 12 19.
Article in English | MEDLINE | ID: mdl-34944092

ABSTRACT

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


Subject(s)
Endoplasmic Reticulum Stress/genetics , Insulin-Secreting Cells/metabolism , Single-Cell Analysis , Transcriptome/genetics , Actin Cytoskeleton/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Humans , Models, Biological , RNA-Seq
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