Related Experiment Video
Updated: Jul 12, 2025
Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells
Published on: September 30, 2018
Single-Cell Transcriptome Profiling of Pancreatic Islets From Early Diabetic Mice Identifies Anxa10 for Ca2+
Kaori Motomura1,2, Takashi Matsuzaka1,3, Shigeyuki Shichino2
1Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Abstract:
Type 2 diabetes is a progressive disorder denoted by hyperglycemia and impaired insulin secretion. Although a decrease in β-cell function and mass is a well-known trigger for diabetes, the comprehensive mechanism is still unidentified. Here, we performed single-cell RNA sequencing of pancreatic islets from prediabetic and diabetic db/db mice, an animal model of type 2 diabetes. We discovered a diabetes-specific transcriptome landscape of endocrine and nonendocrine cell types with subpopulations of β- and α-cells. We recognized a new prediabetic gene, Anxa10, that was induced by and regulated Ca2+ influx from metabolic stresses. Anxa10-overexpressed β-cells displayed suppression of glucose-stimulated intracellular Ca2+ elevation and potassium-induced insulin secretion. Pseudotime analysis of β-cells predicted that this Ca2+-surge responder cluster would proceed to mitochondria dysfunction and endoplasmic reticulum stress. Other trajectories comprised dedifferentiation and transdifferentiation, emphasizing acinar-like cells in diabetic islets. Altogether, our data provide a new insight into Ca2+ allostasis and β-cell failure processes.
Article Highlights:
The transcriptome of single-islet cells from healthy, prediabetic, and diabetic mice was studied. Distinct β-cell heterogeneity and islet cell-cell network in prediabetes and diabetes were found. A new prediabetic β-cell marker, Anxa10, regulates intracellular Ca2+ and insulin secretion. Diabetes triggers β-cell to acinar cell transdifferentiation.
Insights
Researchers identified a new gene, Anxa10, involved in type 2 diabetes progression. This gene impacts calcium regulation and insulin secretion in beta cells, contributing to diabetes development.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Type 2 diabetes is characterized by hyperglycemia and declining beta-cell function.
- The precise mechanisms driving beta-cell failure in diabetes remain incompletely understood.
Purpose of the Study:
- To investigate the single-cell transcriptome landscape of pancreatic islets in prediabetic and diabetic mouse models.
- To identify novel genes and cellular processes contributing to beta-cell dysfunction and diabetes progression.
Main Methods:
- Single-cell RNA sequencing of pancreatic islets from db/db mice (a model for type 2 diabetes).
- Analysis of gene expression, cell subpopulations, and cellular trajectories using pseudotime analysis.
Main Results:
- A distinct transcriptome landscape was observed in diabetic islet cells, including specific beta- and alpha-cell subpopulations.
- A novel prediabetic gene, Anxa10, was identified, regulating calcium influx and suppressing insulin secretion in beta cells.
- Pseudotime analysis indicated that Anxa10-expressing beta cells progress towards mitochondrial dysfunction and endoplasmic reticulum stress.
- Evidence of beta-cell dedifferentiation and transdifferentiation into acinar-like cells was found in diabetic islets.
Conclusions:
- The study provides novel insights into calcium allostasis and beta-cell failure mechanisms in type 2 diabetes.
- Anxa10 emerges as a key regulator of beta-cell function and a potential therapeutic target.
- Cellular plasticity, including transdifferentiation, plays a significant role in diabetes pathogenesis.
