Figure 4.

Specificity of the New Tubular Segments Generated by Zfyve27-CreERT2-Marked Cells during Kidney Repair

(A) Number of tdTomato⁺ cells in Zfyve27-CreERT2;R-tdTomato (n = 8) and Rosa26-CreERT2;R-tdTomato (n = 7) mice 8 days pTM. In the upper papilla, medulla, and cortex both groups had similar cell numbers but in the rest of the papilla, Rosa26-CreERT2;R-tdTomato mice had a much greater number (p < 0.001). Mean ± SE.

(B) Tubules made up of tdTomato cells in injured kidneys (INJ) of Zfyve27-CreERT2;R-tdTomato mice (n = 5; in red) and Rosa26-CreERT2;R-tdTomato mice (n = 6; in green) 8 days after KI, performed 8 days pTM. The average number of tubules per kidney section is shown in the top. Since independently of injury tamoxifen occasionally generated tubules in Rosa26-CreERT2;R-tdTomato mice (Figure S3B′), quantification of the tubules in both the injured (INJ) and non-injured kidneys (CTL, control) is shown. In both mice, KI induced generation of tubules made up of tdTomato⁺ cells (p < 0.0001 versus the control kidney) but the number of tubules in the injured kidney of the Zfyve27-CreERT2;R-tdTomato mice was significantly greater than that in the Rosa26-CreERT2;R-tdTomato mice (p < 0.001). Mean ± SE. The regional distribution of the tubules made up tdTomato⁺ cells is shown in the bottom panel. In the cortex, the number of new tubules was very similar for both groups of mice. In contrast, while the medulla of the Zfyve27-CreERT2;R-tdTomato mice contained 68% of the total number of new kidney tubules, the medulla of the Rosa26-CreERT2;R-tdTomato mice had very few (12%). Mean ± SE.

(C) Tubular structures made up of Zfyve27-CreERT2-marked cells expressing Tamm Horsfall protein (THP). Scale bar, 50 μm.

(D) Tubular structure made up of Zfyve27-CreERT2-marked cells expressing calbindin. Scale bar, 40 μm.

(E) Tubular structures made up of Zfyve27-CreERT2-marked cells expressing megalin. Scale bar, 50 μm.