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

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

doi:10.3390/cells10123585

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

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

6 Citations (Scopus)

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.

Original language	English
Journal	Cells
Volume	10
Issue number	12
DOIs	https://doi.org/10.3390/cells10123585
Publication status	Published - 19 Dec 2021

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title = "Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress",

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.",

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month = dec,

day = "19",

doi = "10.3390/cells10123585",

language = "English",

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journal = "Cells",

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T1 - Single-Cell Transcriptomics Links Loss of Human Pancreatic β-Cell Identity to ER Stress

AU - Groen, Nathalie

AU - Leenders, Floris

AU - Mahfouz, Ahmed

AU - Munoz-Garcia, Amadeo

AU - Muraro, Mauro J

AU - de Graaf, Natascha

AU - Rabelink, Ton J

AU - Hoeben, Rob

AU - van Oudenaarden, Alexander

AU - Zaldumbide, Arnaud

AU - Reinders, Marcel J T

AU - Koning, Eelco J P de

AU - Carlotti, Françoise

PY - 2021/12/19

Y1 - 2021/12/19

N2 - 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.

AB - 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.

U2 - 10.3390/cells10123585

DO - 10.3390/cells10123585

M3 - Article

C2 - 34944092

SN - 2073-4409

VL - 10

JO - Cells

JF - Cells

IS - 12

ER -

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

Abstract

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