Add like
Add dislike
Add to saved papers

Taxonomy of fibroblasts and progenitors in the synovial joint at single-cell resolution.

OBJECTIVES: Fibroblasts in synovium include fibroblast-like synoviocytes (FLS) in the lining and Thy1 + connective-tissue fibroblasts in the sublining. We aimed to investigate their developmental origin and relationship with adult progenitors.

METHODS: To discriminate between Gdf5 -lineage cells deriving from the embryonic joint interzone and other Pdgfrα -expressing fibroblasts and progenitors, adult Gdf5-Cre;Tom;Pdgfrα-H2BGFP mice were used and cartilage injury was induced to activate progenitors. Cells were isolated from knees, fibroblasts and progenitors were sorted by fluorescence-activated cell-sorting based on developmental origin, and analysed by single-cell RNA-sequencing. Flow cytometry and immunohistochemistry were used for validation. Clonal-lineage mapping was performed using Gdf5-Cre;Confetti mice.

RESULTS: In steady state, Thy1 + sublining fibroblasts were of mixed ontogeny. In contrast, Thy1-Prg4 + lining fibroblasts predominantly derived from the embryonic joint interzone and included Prg4 -expressing progenitors distinct from molecularly defined FLS. Clonal-lineage tracing revealed compartmentalisation of Gdf5 -lineage fibroblasts between lining and sublining. Following injury, lining hyperplasia resulted from proliferation and differentiation of Prg4 -expressing progenitors, with additional recruitment of non- Gdf5 -lineage cells, into FLS. Consistent with this, a second population of proliferating cells, enriched near blood vessels in the sublining, supplied activated multipotent cells predicted to give rise to Thy1 + fibroblasts, and to feed into the FLS differentiation trajectory. Transcriptional programmes regulating fibroblast differentiation trajectories were uncovered, identifying Sox5 and Foxo1 as key FLS transcription factors in mice and humans.

CONCLUSIONS: Our findings blueprint a cell atlas of mouse synovial fibroblasts and progenitors in healthy and injured knees, and provide novel insights into the cellular and molecular principles governing the organisation and maintenance of adult synovial joints.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app