Cellular diversity of the regenerating caudal fin

Abstract

Zebrafish faithfully regenerate their caudal fin after amputation. During this process, both differentiated cells and resident progenitors migrate to the wound site and undergo lineage-restricted, programmed cellular state transitions to populate the new regenerate. Until now, systematic characterizations of cells comprising the new regenerate and molecular definitions of their state transitions have been lacking. We hereby characterize the dynamics of gene regulatory programs during fin regeneration by creating single-cell transcriptome maps of both preinjury and regenerating fin tissues at 1/2/4 days post-amputation. We consistently identified epithelial, mesenchymal, and hematopoietic populations across all stages. We found common and cell type–specific cell cycle programs associated with proliferation. In addition to defining the processes of epithelial replenishment and mesenchymal differentiation, we also identified molecular signatures that could better distinguish epithelial and mesenchymal subpopulations in fish. The insights for natural cell state transitions during regeneration point to new directions for studying this regeneration model.

Single-cell resolution of MET- and EMT-like programs in osteoblasts during zebrafish fin regeneration

“…We also identified genes with significantly increased expression in 3). This included cdh11 (Fig 1H ), which was recently identified by scRNA-seq to be a potential marker of osteoblastic cells, but still remains to be validated [18]. We concluded that osteoblast1 and osteoblast2 were enriched for cells fated to become osteoblasts and joint cells, respectively.…”

“…As such, more in-depth molecular characterizations are needed. While single cell analyses are comprehensive approaches and can provide valuable insight, previous single-cell RNA-seq (scRNA-seq) studies of zebrafish caudal fin regeneration have reported low numbers of osteoblastic cells [18], preventing an in-depth analysis of E and M characteristics.…”

Dynamics of repair and regeneration of adult zebrafish respiratory gill tissue after cryoinjury.

“…Fibin transcripts are also decreased in lung samples of mice exposed to house dust mite, Toxoplasma, or influenza, RSV, and SARS-Cov viruses. Analysis of single cell RNA seq datasets in zebrafish (caudal fin; [64]) and the human lung (IPFcellatlas.com) also revealed that zebrafish fibina, fibinb and human FIBIN are expressed in the mesenchymal lineage, specifically in fibroblasts (not shown). Consistent with the expression of FIBIN in lung fibroblasts and with the decrease of Fibin transcripts in mouse models of lung damage, we found that mesenchymal FIBIN expression is decreased in lung samples from patients with chronic lung conditions such as IPF and asthma (Fig.…”

The engine initiating tissue regeneration: does a common mechanism exist during evolution?

“…Moreover, establishing new experimental systems to segregate wound healing and the onset of tissue regeneration will also be valuable. Furthermore, emerging new technologies, such as single cell sequencing and various “omics”, have already been applied to regenerative species such as axolotls and zebrafish (Gerber et al 2018 ; Leigh et al 2018 ; Hoang et al 2020 ; Hou et al 2020 ; Li et al 2020 ), and will contribute to in-depth study of the current unresolved issues in the field of regeneration.…”