Single-Cell Transcriptome Profiling of Pancreatic Islets From Early Diabetic Mice Identifies Anxa10 for Ca2+...

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.