| First Author | Harvey T | Year | 2019 |
| Journal | Nat Cell Biol | Volume | 21 |
| Issue | 12 | Pages | 1490-1503 |
| PubMed ID | 31768046 | Mgi Jnum | J:282887 |
| Mgi Id | MGI:6384107 | Doi | 10.1038/s41556-019-0417-z |
| Citation | Harvey T, et al. (2019) A Tppp3(+)Pdgfra(+) tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis. Nat Cell Biol 21(12):1490-1503 |
| abstractText | Tendon injuries cause prolonged disability and never recover completely. Current mechanistic understanding of tendon regeneration is limited. Here, we use single-cell transcriptomics to identify a tubulin polymerization-promoting protein family member 3-expressing (Tppp3(+)) cell population as potential tendon stem cells. Through inducible lineage tracing, we demonstrate that these cells can generate new tenocytes and self-renew upon injury. A fraction of Tppp3(+) cells expresses platelet-derived growth factor receptor alpha (Pdfgra). Ectopic platelet-derived growth factor-AA (PDGF-AA) protein induces new tenocyte production while inactivation of Pdgfra in Tppp3(+) cells blocks tendon regeneration. These results support Tppp3(+)Pdgfra(+) cells as tendon stem cells. Unexpectedly, Tppp3(-)Pdgfra(+) fibro-adipogenic progenitors coexist in the tendon stem cell niche and give rise to fibrotic cells, revealing a clandestine origin of fibrotic scars in healing tendons. Our results explain why fibrosis occurs in injured tendons and present clinical challenges to enhance tendon regeneration without a concurrent increase in fibrosis by PDGF application. |
