Figure 1. S100a4 is expressed by resident tenocytes and the S100a4⁺cell population expands during tendon healing.

(A and B) S100a4-Cre; Rosa-Ai9 reporter mice demonstrate efficient targeting of resident tendon cells. Following injury, the S100a4-lineage (S100a4^Lin+) population expands, with S100a4^Lin+ cells in the native tendon stubs and the bridging scar tissue at D7 and D14 post-surgery. Tendons are outlined in white, and bridging granulation tissue outlined in blue. (C) Quantification of S100a4^Lin+ area over time. (*) indicates p<0.05 (1-way ANOVA). (D) The S100a4-GFP^promoter construct identifies cells actively expressing S100a4 (S100a4-GFP^promoter+). (E) A subpopulation of resident tenocytes is S100a4-GFP^promoter+ at baseline, and the S100a4-GFP^promoter+ population increases following injury, with S100a4-GFP^promoter+ cells observed in the bridging scar tissue and native tendon ends through D28 post-surgery. Tendons are outlined in white, and bridging granulation tissue outlined in orange, (*) identifies sutures. (F) Quantification of the S100a4-GFP^promoter+ area over time. (*) indicates p<0.05 (1-way ANOVA). (G) qPCR analysis of S100a4 during tendon healing demonstrates peak S100a4 expression at D10, followed by a progressive decline through D28 (n = 3 per time-point). (*) indicates p<0.05 vs. D3 repair (1-way ANOVA). Data were normalized to expression in D3 repairs, and the internal control β-actin.

Figure 1—figure supplement 1. S100a4⁺cells are found in the healthy and healing Achilles tendon.

S100a4-GFP^Promoter+ cells are observed in the native Achilles tendon, and a S100a4⁺ population persists following complete transection and repair of the Achilles tendon at D14 post-surgery.