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|Public on Nov 27, 2023
|Effect of DRG conditioned media on Tppp3+ tendon cells
|Expression profiling by high throughput sequencing
|Here, we investigated the effect of conditioned media (CM) obtained from cultured mouse DRG neurons on Tppp3+ cells, mainly on proliferation and differentiation potential. Peripheral afferent neurons terminate at the surfaces of tendons, yet their role after injury beyond nociceptive functions remain unclear. Using transgenic animal models, sensory neurons were found to sprout after Achilles tendon injury in domains of Nerve growth factor (NGF) expression. Conditional deletion of Ngf in either myeloid or mesenchymal cell types led to tendon repair defects – findings phenocopied by inactivation of TrkA (Tropomyosin receptor kinase A) using a knockin mouse model. A combination of spatial and single cell transcriptomics revealed dysregulated inflammatory and TGF signaling upon lack of neural input. Utilizing sural nerve transection in reporter animals, we identified that neural input is required for proper expansion of Tppp3+ tendon sheath progenitor cells (TSPCs) after injury, and in vitro approaches implicated TGF signaling activation in Tppp3+ TSPC neural response. Finally, in a translational approach, activation of TrkA+ sensory neurons using a partial agonist led to a significant increase in TGF signaling, TSPC expansion, and improved tendon repair. Collectively, these data implicate peripheral afferent neural networks in the coordinated acute tendon injury response, and identify candidate molecules to speed the reparative process.
|Bulk RNA sequencing of mice achiles tendon Tppp3+ cells with DRG CM or 1% FBS media at 24 h. Three biological replicates for experimental Tppp3+ cells with DRG CM were compared with three biological replicates Tppp3+ cells with 1% FBS media controls.
|Cherief M, James A
|Dec 15, 2022
|Last update date
|Nov 27, 2023
|Johns Hopkins University
|720 Rutland Avenue, Ross Bldg., Room 529
|Illumina NovaSeq 6000 (Mus musculus)
|This SubSeries is part of SuperSeries: