| Autor: |
Ciro Salinno, Maren Büttner, Perla Cota, Sophie Tritschler, Marta Tarquis-Medina, Aimée Bastidas-Ponce, Katharina Scheibner, Ingo Burtscher, Anika Böttcher, Fabian J. Theis, Mostafa Bakhti, Heiko Lickert |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Molecular Metabolism, Vol 49, Iss , Pp 101188- (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2212-8778 |
| DOI: |
10.1016/j.molmet.2021.101188 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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