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

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Item Type:Article
Title:A single-cell atlas of de novo β-cell regeneration reveals the contribution of hybrid β/δ-cells to diabetes recovery in zebrafish
Creators Name:Singh, S.P. and Chawla, P. and Hnatiuk, A. and Kamel, M. and Silva, L.D. and Spanjaard, B. and Eski, S.E. and Janjuha, S. and Olivares-Chauvet, P. and Kayisoglu, O. and Rost, F. and Bläsche, J. and Kränkel, A. and Petzold, A. and Kurth, T. and Reinhardt, S. and Junker, J.P. and Ninov, N.
Abstract: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.
Keywords:Beta-Cell, Insulin, Pancreas, Regeneration, Single Cell, Gamma-Cell, Cell Fate, Cell Plasticity, Diabetes, Animals, Zebrafish
Publisher:Company of Biologists
Page Range:dev199853
Date:January 2022
Additional Information:Copyright © 2022 The Author(s). Published by The Company of Biologists Ltd
Official Publication:https://doi.org/10.1242/dev.199853
PubMed:View item in PubMed

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