Single-cell resolution of MET- and EMT-like programs in osteoblasts during zebrafish fin regeneration
W. Joyce Tang,
Claire J. Watson,
Theresa Olmstead,
Christopher H. Allan,
Ronald Y. Kwon
Affiliations
W. Joyce Tang
Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, WA 98105, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA; Corresponding author
Claire J. Watson
Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, WA 98105, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA
Theresa Olmstead
Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, WA 98105, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA
Christopher H. Allan
Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, WA 98105, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA
Ronald Y. Kwon
Department of Orthopaedics and Sports Medicine, University of Washington School of Medicine, Seattle, WA 98105, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98109, USA
Summary: Zebrafish regenerate fin rays following amputation through epimorphic regeneration, a process that has been proposed to involve the epithelial-to-mesenchymal transition (EMT). We performed single-cell RNA sequencing (scRNA-seq) to elucidate osteoblastic transcriptional programs during zebrafish caudal fin regeneration. We show that osteoprogenitors are enriched with components associated with EMT and its reverse, mesenchymal-to-epithelial transition (MET), and provide evidence that the EMT markers cdh11 and twist2 are co-expressed in dedifferentiating cells at the amputation stump at 1 dpa, and in differentiating osteoblastic cells in the regenerate, the latter of which are enriched in EMT signatures. We also show that esrp1, a regulator of alternative splicing in epithelial cells that is associated with MET, is expressed in a subset of osteoprogenitors during outgrowth. This study provides a single cell resource for the study of osteoblastic cells during zebrafish fin regeneration, and supports the contribution of MET- and EMT-associated components to this process.