Single-cell transcriptomics links loss of human pancreatic β-cell identity to er stress

Single-cell transcriptomics links loss of human pancreatic β-cell identity to er stress

Groen, Nathalie (Leiden University Medical Center)
Leenders, Floris (Leiden University Medical Center)
Mahfouz, A.M.E.T.A. (TU Delft Pattern Recognition and Bioinformatics; Leiden University Medical Center)
Munoz-Garcia, Amadeo (Leiden University Medical Center)
Muraro, Mauro J. (University Medical Center Utrecht)
de Graaf, Natascha (Leiden University Medical Center)
Rabelink, Ton J. (Leiden University Medical Center)
Hoeben, Rob (Leiden University Medical Center)
Reinders, M.J.T. (TU Delft Pattern Recognition and Bioinformatics; Leiden University Medical Center)

2021

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 illus-trate 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.

ER stress
Human pancreatic islets
Islet integrity
Single-cell RNAseq
Type 2 diabetes
β-cells

http://resolver.tudelft.nl/uuid:3396118b-382b-407f-b3bb-d03b20c7d253

https://doi.org/10.3390/cells10123585

2073-4409

Cells, 10 (12)

Institutional Repository

journal article

© 2021 Nathalie Groen, Floris Leenders, A.M.E.T.A. Mahfouz, Amadeo Munoz-Garcia, Mauro J. Muraro, Natascha de Graaf, Ton J. Rabelink, Rob Hoeben, M.J.T. Reinders, More Authors