Datasets

Title	Adaptation to chronic ER stress enforces pancreatic beta-cell plasticity
Organism
Number of Samples	9
Release Date	2021/05/19 00:00
Sequencing Types
Protocol Details

Title
Authors	Chen CW,Guan BJ,Alzahrani MR,Gao Z,Gao L,Bracey S,Wu J,Mbow CA,Jobava R,Haataja L,Zalavadia AH,Schaffer AE,Lee H,LaFramboise T,Bederman I,Arvan P,Mathews CE,Gerling IC,Kaestner KH,Tirosh B,Engin F,Hatzoglou M
Journal	Nature communications
Publication Date	2022 Aug 8
Abstract	Pancreatic β-cells are prone to endoplasmic reticulum (ER) stress due to their role in insulin secretion. They require sustainable and efficient adaptive stress responses to cope with this stress. Whether episodes of chronic stress directly compromise β-cell identity is unknown. We show here under reversible, chronic stress conditions β-cells undergo transcriptional and translational reprogramming associated with impaired expression of regulators of β-cell function and identity. Upon recovery from stress, β-cells regain their identity and function, indicating a high degree of adaptive plasticity. Remarkably, while β-cells show resilience to episodic ER stress, when episodes exceed a threshold, β-cell identity is gradually lost. Single cell RNA-sequencing analysis of islets from type 1 diabetes patients indicates severe deregulation of the chronic stress-adaptation program and reveals novel biomarkers of diabetes progression. Our results suggest β-cell adaptive exhaustion contributes to diabetes pathogenesis. © 2022. The Author(s).
PMC	PMC9360004
PMID	35941159
DOI

Chen et al. 2021 (PRJNA731067)