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Salinno, C. ; Büttner, M. ; Cota, P. ; Tritschler, S. ; Tarquis-Medina, M. ; Bastidas-Ponce, A. ; Scheibner, K. ; Burtscher, I. ; Böttcher, A. ; Theis, F.J. ; Bakhti, M. ; Lickert, H.

CD81 marks immature and dedifferentiated pancreatic β-cells.

Mol. Metab. 49:101188 (2021)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cd81 ; Dedifferentiation ; Heterogeneity ; Immature ; Maturation ; β-cells; Insulin-secretion; Maturation; Expression; Establishment; Islets; Line; Heterogeneity; Plasticity; Triggers; Dynamics

ISSN (print) / ISBN 2212-8778

e-ISSN 2212-8778

Journal Molecular Metabolism

Quellenangaben Volume: 49, Article Number: 101188

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)

Grants Deutsches Zentrum fur Diabetesforschung (DZD)
HelmholtzGemeinschaft (Helmholtz Portfolio Theme Metabolic Dysfunction and Common Disease)