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

• DOI: 10.1242/dev.199853
• Publication Date: 2022-01-28T11:10:31Z
• Authors: Sumeet Pal Singh; Prateek Chawla; Alisa Hnatiuk; Margrit Kamel; Luis Delgadillo S...; Bastiaan Spanjaard; Sema Elif Eski; Sharan Janjuha; Pedro Olivares-Ch...; Oezge Kayisoglu; Fabian Rost; Juliane Bläsche; Annekathrin Kränkel; Andreas Petzold; Thomas Kurth; Susanne Reinhardt; Jan Philipp Junker; Nikolay Ninov
• Keywords: Cell type

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