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

Research output: Contribution to journalResearch articleContributedpeer-review



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.


Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalDevelopment (Cambridge)
Issue number2
Publication statusPublished - 15 Jan 2022

External IDs

Scopus 85124446327
unpaywall 10.1242/dev.199853
WOS 000759115300013
Mendeley 515989c4-717e-3e9c-8f23-fc5809b1211f
ORCID /0000-0001-6466-2589/work/142238089
ORCID /0000-0001-5624-1717/work/142239000
ORCID /0000-0001-9599-8632/work/142241731


DFG Classification of Subject Areas according to Review Boards

Sustainable Development Goals


  • Animals, Calcium/metabolism, Diabetes Mellitus/metabolism, Glucose/metabolism, Insulin/metabolism, Insulin-Secreting Cells/cytology, Regeneration, Single-Cell Analysis, Somatostatin-Secreting Cells/cytology, Zebrafish, Beta-cell, Single cell, Gamma-cell, Insulin, Cell plasticity, Cell fate, Diabetes, Pancreas, Migration, Vessel remodelling, Human, Proliferation, WASp, F-actin, Shear stress

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