biostudies-literatureUnknown9(46)Rajan AMDespite their importance in tissue maintenance and repair, fibroblast diversity and plasticity remain poorly understood. Using single-cell RNA sequencing, we uncover distinct sclerotome-derived fibroblast populations in zebrafish, including progenitor-like perivascular/interstitial fibroblasts, and specialized fibroblasts such as tenocytes. To determine fibroblast plasticity in vivo, we develop a laser-induced tendon ablation and regeneration model. Lineage tracing reveals that laser-ablated tenocytes are quickly regenerated by preexisting fibroblasts. By combining single-cell clonal analysis and live imaging, we demonstrate that perivascular/interstitial fibroblasts actively migrate to the injury site, where they proliferate and give rise to new tenocytes. By contrast, perivascular fibrobScience advanceseadi5771https://www.ebi.ac.uk/biostudies/studies/S-EPMC10651129biostudies-literatureSingle-cell analysis reveals distinct fibroblast plasticity during tenocyte regeneration in zebrafish.PMC10651129Rajan AMRosin NLBiernaskie JLabit ELiao SHuang PfalseSingle-cell analysis reveals distinct fibroblast plasticity during tenocyte regeneration in zebrafish.Despite their importance in tissue maintenance and repair, fibroblast diversity and plasticity remain poorly understood. Using single-cell RNA sequencing, we uncover distinct sclerotome-derived fibroblast populations in zebrafish, including progenitor-like perivascular/interstitial fibroblasts, and specialized fibroblasts such as tenocytes. To determine fibroblast plasticity in vivo, we develop a laser-induced tendon ablation and regeneration model. Lineage tracing reveals that laser-ablated tenocytes are quickly regenerated by preexisting fibroblasts. By combining single-cell clonal analysis and live imaging, we demonstrate that perivascular/interstitial fibroblasts actively migrate to the injury site, where they proliferate and give rise to new tenocytes. By contrast, perivascular fibrob2023-01-01T00:00:00Z2023 Nov2025-04-19T16:14:46.602Z2025-04-19T16:14:46.602ZS-EPMC106511293796718010.1126/sciadv.adi5771