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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)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
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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 (CD81high) compared to a more mature population expressing no or low levels of this protein (CD81low/-). 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
Keywords Cd81 ; Dedifferentiation ; Heterogeneity ; Immature ; Maturation ; β-cells; Insulin-secretion; Maturation; Expression; Establishment; Islets; Line; Heterogeneity; Plasticity; Triggers; Dynamics
Language english
Publication Year 2021
HGF-reported in Year 2021
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Journal Molecular Metabolism
Quellenangaben Volume: 49, Issue: , Pages: , Article Number: 101188 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Computational Biology (ICB)
POF-Topic(s) 30201 - Metabolic Health
90000 - German Center for Diabetes Research
30205 - Bioengineering and Digital Health
Research field(s) Helmholtz Diabetes Center
Enabling and Novel Technologies
PSP Element(s) G-502300-001
G-501900-231
G-503800-001
Grants Deutsches Zentrum fur Diabetesforschung (DZD)
HelmholtzGemeinschaft (Helmholtz Portfolio Theme Metabolic Dysfunction and Common Disease)
DOI 10.1016/j.molmet.2021.101188
WOS ID WOS:000667760600001
Scopus ID 85101778582
PubMed ID 33582383
Erfassungsdatum 2021-05-11
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