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Singh, S.P.* ; Chawla, P.* ; Hnatiuk, A.* ; Kamel, M.* ; Silva, L.D.* ; Spanjaard, B.* ; Eski, S.E.* ; Janjuha, S.* ; Olivares-Chauvet, P.* ; Kayisoglu, O.* ; Rost, F.* ; Bläsche, J.* ; Kränkel, A.* ; Petzold, A.* ; Kurth, T.* ; Reinhardt, S.* ; Junker, J.P.* ; Ninov, N.

A single-cell atlas of de novo β-cell regeneration reveals the contribution of hybrid β/δ-cells to diabetes recovery in zebrafish.

Development 149:dev199853 (2022)

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Regeneration-competent species possess the ability to reverse the progression of severe diseases by restoring the function of the damaged tissue. However, the cellular dynamics underlying this capability remain unexplored. Here, we have used single-cell transcriptomics to map de novo β-cell regeneration during induction and recovery from diabetes in zebrafish. We show that the zebrafish has evolved two distinct types of somatostatin-producing δ-cells, which we term δ1- and δ2-cells. Moreover, we characterize a small population of glucose-responsive islet cells, which share the hormones and fate-determinants of both β- and δ1-cells. The transcriptomic analysis of β-cell regeneration reveals that β/δ hybrid cells provide a prominent source of insulin expression during diabetes recovery. Using in vivo calcium imaging and cell tracking, we further show that the hybrid cells form de novo and acquire glucose-responsiveness in the course of regeneration. The overexpression of dkk3, a gene enriched in hybrid cells, increases their formation in the absence of β-cell injury. Finally, interspecies comparison shows that plastic δ1-cells are partially related to PP cells in the human pancreas. Our work provides an atlas of β-cell regeneration and indicates that the rapid formation of glucose-responsive hybrid cells contributes to the resolution of diabetes in zebrafish.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Beta-cell ; Cell Fate ; Cell Plasticity ; Diabetes ; Gamma-cell ; Insulin ; Pancreas ; Regeneration ; Single Cell ; Zebrafish; Transgenic Zebrafish; Pancreatic-islets; Expression; Insulin; Fate; Differentiation; Generation; Progenitor; Conversion; Proteins

ISSN (print) / ISBN 0950-1991

e-ISSN 1477-9129

Journal Development / Company of Biologists

Quellenangaben Volume: 149, Issue: 2, Article Number: dev199853

Publisher Company of Biologists

Publishing Place Bidder Building, Station Rd, Histon, Cambridge Cb24 9lf, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Pancreatic Beta Cell Research (IPI)

Grants International Research Training Group (IRTG 2251): 'Immunological and Cellular Strategies in Metabolic Disease'
Deutsche Forschungsgemeinschaft
Deutsches Zentrum fur Diabetesforschung (DZD)
Center for Regenerative Therapies Dresden at Technische Universitat Dresden
Fonds de la Recherche Scientifique-FNRS
European Research Council starting grant