Dynamic cell fate plasticity and tissue reintegration drive functional adult synovial joint regeneration after complete resection

Maria Blumenkrantz, Felicia Woron, Ernesto Gagarin, Everett Weinstein, Maryam H. Kamel, Leonardo Campos, Agnieszka Geras, Troy Anderson, Julia Mo, Desmarie Sherwood, Maya Gwin, Bianca Dumitrascu, Nadeen O. Chahine and Joanna Smeeton ()
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Maria Blumenkrantz: Columbia University
Felicia Woron: Columbia University
Ernesto Gagarin: Columbia University
Everett Weinstein: Columbia University
Maryam H. Kamel: Columbia University
Leonardo Campos: Columbia University
Agnieszka Geras: Columbia University
Troy Anderson: Columbia University
Julia Mo: Columbia University
Desmarie Sherwood: Columbia University
Maya Gwin: Columbia University
Bianca Dumitrascu: Columbia University
Nadeen O. Chahine: Columbia University
Joanna Smeeton: Columbia University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract 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.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63596-8

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DOI: 10.1038/s41467-025-63596-8

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