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Single-Cell Transcriptional Profiling of Mouse Islets Following Short-Term ObesogenicDietary Intervention

ABSTRACT: Obesity is closely associated with adipose tissue inflammation and insulin resistance. Dysglycemia and type 2 diabetes results when islet β cells fail to maintain appropriate insulin secretion in the face of insulin resistance. To clarify the early transcriptional events leading to β-cell failure in the setting of obesity, we fed male C57BL/6J mice an obesogenic, high fat diet (60% kcal from fat) or control diet (10% kcal from fat) for one week and islets from these mice (from 4 high fat- and 3 control-fed mice) were subjected to single cell RNA sequencing analysis. Islet endocrine cell types (α cells, β cells, δ cells, PP cells) and other resident cell types (macrophages, T cells) were annotated by transcript profiles and visualized using Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP) plots. UMAP analysis revealed distinct cell sub-populations (11 for β cells, 5 for α cells, 3 for δ cells, PP cells, ductal cells, endothelial cells), emphasizing the heterogeneity of cell populations in the islet. We identified that distinct β cell populations downregulate genes associated with the endoplasmic reticulum stress response and upregulate genes associated with insulin secretion, while others upregulate genes that impair insulin secretion, cellular proliferation, and survival. Moreover, all β cell populations negatively regulate genes associated with immune response activation. Our data indicate that an early transcriptional response in islets to an obesogenic diet reflects an attempt by distinct populations of β cells to augment or impair cellular function, possible harbingers of ensuing insulin resistance.

ORGANISM(S): Mus musculus

PROVIDER: GSE162512 | GEO | 2020/12/03

REPOSITORIES: GEO

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