Dynamic cell fate plasticity and tissue integration drive functional synovial joint regeneration
Blumenkrantz, M.; Woron, F.; Gagarin, E.; Weinstein, E.; Kamel, M. H.; Campos, L.; Geras, A.; Anderson, T.; Mo, J.; Sherwood, D.; Gwin, M.; Dumitrascu, B.; Chahine, N. O.; Smeeton, J.
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Adult mammalian synovial joints have limited regenerative capacity, where injuries heal with mechanically inferior fibrotic tissues. Here we developed a unilateral whole-joint resection model in adult zebrafish to advance our understanding of how to stimulate regrowth of native synovial joint tissues. Using a combination of microCT, histological, live imaging, and single-cell RNA sequencing (scRNAseq) approaches after complete removal of all joint tissues, we find de novo regeneration of articular cartilage, ligament, and synovium into a functional joint. Clonal lineage tracing and scRNAseq implicate a multipotent, neural crest-derived population in the adult skeleton as a cell source for these regenerating tissues. Together, our findings reveal latent molecular and cellular programs within the adult skeleton that are deployed to regenerate a complex joint with lubricated articular cartilage.
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