Dataset Information


A Tppp3+Pdgfra+ tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis.

ABSTRACT: 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.


PROVIDER: S-EPMC6895435 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC7324157 | BioStudies
1000-01-01 | S-EPMC4563693 | BioStudies
2020-01-01 | S-EPMC7055210 | BioStudies
2021-01-01 | S-EPMC7910464 | BioStudies
2014-01-01 | S-EPMC3929697 | BioStudies
2014-01-01 | S-EPMC4080701 | BioStudies
2019-01-01 | S-EPMC6318926 | BioStudies
2020-01-01 | S-EPMC7307866 | BioStudies
2017-01-01 | S-EPMC5702462 | BioStudies
2013-01-01 | S-EPMC3875481 | BioStudies