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

Author

Listed:
  • 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
    Columbia University)

  • Agnieszka Geras

    (Columbia University)

  • Troy Anderson

    (Columbia University
    Columbia University)

  • Julia Mo

    (Columbia University
    Columbia University)

  • Desmarie Sherwood

    (Columbia University)

  • Maya Gwin

    (Columbia University
    Marymount School of New York)

  • Bianca Dumitrascu

    (Columbia University
    Columbia University)

  • Nadeen O. Chahine

    (Columbia University
    Columbia University)

  • Joanna Smeeton

    (Columbia University
    Columbia University)

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.

Suggested Citation

  • Maria Blumenkrantz & Felicia Woron & Ernesto Gagarin & Everett Weinstein & Maryam H. Kamel & Leonardo Campos & Agnieszka Geras & Troy Anderson & Julia Mo & Desmarie Sherwood & Maya Gwin & Bianca Dumit, 2025. "Dynamic cell fate plasticity and tissue reintegration drive functional adult synovial joint regeneration after complete resection," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63596-8
    DOI: 10.1038/s41467-025-63596-8
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