Fig. 7: A single-cell analysis of the mouse tendon illuminates the key role of Axin2⁺ cells as central organizers of tendon healing.

Cartoon depiction of the identified cell types in the tendon during homeostasis and injury with a focus on relevant clusters (A). In our model, B Axin2⁺/Scx⁺ tendon cells require their own Wnt signal to maintain their Procr/CD201⁺ and Axin2⁺ state in homeostasis. Upon injury, our single-cell RNA-seq and genetic lineage tracing show that Axin2⁺ cells adopt an injury-responsive state (IRC-1 and IRC-2), expressing Sox9 and Acta2. They robustly migrate, proliferate, adopt a rounded morphology, and then differentiate into tenocytes expressing common markers of tendon fate (Scx, Col1a1, and Tnmd). These processes are entirely dependent upon the secretion of their own Wnt ligands, likely Wnt9a.