Identification of unique cell type responses in pancreatic islets to stress.
Nat Commun
; 15(1): 5567, 2024 Jul 02.
Article
em En
| MEDLINE
| ID: mdl-38956087
ABSTRACT
Diabetes involves the death or dysfunction of pancreatic ß-cells. Analysis of bulk sequencing from human samples and studies using in vitro and in vivo models suggest that endoplasmic reticulum and inflammatory signaling play an important role in diabetes progression. To better characterize cell type-specific stress response, we perform multiplexed single-cell RNA sequencing to define the transcriptional signature of primary human islet cells exposed to endoplasmic reticulum and inflammatory stress. Through comprehensive pair-wise analysis of stress responses across pancreatic endocrine and exocrine cell types, we define changes in gene expression for each cell type under different diabetes-associated stressors. We find that ß-, α-, and ductal cells have the greatest transcriptional response. We utilize stem cell-derived islets to study islet health through the candidate gene CIB1, which was upregulated under stress in primary human islets. Our findings provide insights into cell type-specific responses to diabetes-associated stress and establish a resource to identify targets for diabetes therapeutics.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ilhotas Pancreáticas
/
Células Secretoras de Insulina
/
Estresse do Retículo Endoplasmático
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article