Pancreatic β-Cell Identity Change through the Lens of Single-Cell Omics Research

• Published in: International journal of molecular sciences 2024-05, Vol.25 (9), p.4720
• Main Authors: Leenders, Floris, de Koning, Eelco J P, Carlotti, Françoise
• Format: Article
• Language: English
• Subjects: Animals; Cell death; Cells; Chromatin; Development and progression; Diabetes; diabetes mellitus; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Endoplasmic Reticulum Stress - genetics; Genes; Genetic transcription; Genomics; Genomics - methods; Glucagon; Glucose; Humans; Insulin; Insulin resistance; Insulin-Secreting Cells - metabolism; Physiology; RNA; Single-Cell Analysis - methods; single-cell omics research; Type 2 diabetes; β-cell dedifferentiation; β-cell heterogeneity; β-cell identity change; β-cell subpopulations
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25094720

The main hallmark in the development of both type 1 and type 2 diabetes is a decline in functional β-cell mass. This decline is predominantly attributed to β-cell death, although recent findings suggest that the loss of β-cell identity may also contribute to β-cell dysfunction. This phenomenon is characterized by a reduced expression of key markers associated with β-cell identity. This review delves into the insights gained from single-cell omics research specifically focused on β-cell identity. It highlights how single-cell omics based studies have uncovered an unexpected level of heterogeneity among β-cells and have facilitated the identification of distinct β-cell subpopulations through the discovery of cell surface markers, transcriptional regulators, the upregulation of stress-related genes, and alterations in chromatin activity. Furthermore, specific subsets of β-cells have been identified in diabetes, such as displaying an immature, dedifferentiated gene signature, expressing significantly lower insulin mRNA levels, and expressing increased β-cell precursor markers. Additionally, single-cell omics has increased insight into the detrimental effects of diabetes-associated conditions, including endoplasmic reticulum stress, oxidative stress, and inflammation, on β-cell identity. Lastly, this review outlines the factors that may influence the identification of β-cell subpopulations when designing and performing a single-cell omics experiment.