CD81 marks immature and dedifferentiated pancreatic β-cells

Salinno C, Buettner M, Cota P, Tritschler S, Tarquis-Medina M, Bastidas-Ponce A, Scheibner K, Burtscher I, Boettcher A, Theis FJ, Bakhti M, Lickert H (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Molecular Metabolism Elsevier

Book Volume: 49

Article Number: 101188

DOI: 10.1016/j.molmet.2021.101188

Abstract

Objective: Islets of Langerhans contain heterogeneous populations of insulin-producing β-cells. Surface markers and respective antibodies for isolation, tracking, and analysis are urgently needed to study β-cell heterogeneity and explore the mechanisms to harness the regenerative potential of immature β-cells. Methods: We performed single-cell mRNA profiling of early postnatal mouse islets and re-analyzed several single-cell mRNA sequencing datasets from mouse and human pancreas and islets. We used mouse primary islets, iPSC-derived endocrine cells, Min6 insulinoma, and human EndoC-βH1 β-cell lines and performed FAC sorting, Western blotting, and imaging to support and complement the findings from the data analyses. Results: We found that all endocrine cell types expressed the cluster of differentiation 81 (CD81) during pancreas development, but the expression levels of this protein were gradually reduced in β-cells during postnatal maturation. Single-cell gene expression profiling and high-resolution imaging revealed an immature signature of β-cells expressing high levels of CD81 (CD81^high) compared to a more mature population expressing no or low levels of this protein (CD81^low/-). Analysis of β-cells from different diabetic mouse models and in vitro β-cell stress assays indicated an upregulation of CD81 expression levels in stressed and dedifferentiated β-cells. Similarly, CD81 was upregulated and marked stressed human β-cells in vitro. Conclusions: We identified CD81 as a novel surface marker that labels immature, stressed, and dedifferentiated β-cells in the adult mouse and human islets. This novel surface marker will allow us to better study β-cell heterogeneity in healthy subjects and diabetes progression.

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich

Germany (DE)

How to cite

APA:

Salinno, C., Buettner, M., Cota, P., Tritschler, S., Tarquis-Medina, M., Bastidas-Ponce, A.,... Lickert, H. (2021). CD81 marks immature and dedifferentiated pancreatic β-cells. Molecular Metabolism, 49. https://doi.org/10.1016/j.molmet.2021.101188

MLA:

Salinno, Ciro, et al. "CD81 marks immature and dedifferentiated pancreatic β-cells." Molecular Metabolism 49 (2021).

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