Fig. 1: YAP/TAZ hyperactivation in PDGFRβ+ IntSCs induces lacteal sprouting and branching.

a Diagram depicting the generation of Lats1/2iΔPβC mouse and PDGFRβ+ cell-specific depletion of Lats1/2 in 8-week-old mice and analyses at 2 weeks later. b, c Representative images of LYVE-1+ lacteals and CD31+ capillary plexus under the E-cadherin+ epithelial cells in intestinal villi of the indicated part of small intestine and comparisons of the lacteal surface area per villi, lacteal length, villi length, and villi width in the duodenum (DD), jejunum (JJ), and ileum (IL) in WT and Lats1/2iΔPβC mice. Dots indicate values of 101–217 villi/group in n = 5 mice/group pooled from three independent experiments. Horizontal bars indicate mean ± SD and *** P < 0.0001 versus WT by two-tailed Mann–Whitney U test. n.s., not significant. Scale bars, 100 μm. d, e Representative images and comparisons of the number of lacteal sprouts and branches per 100 μm of lacteal length in WT and Lats1/2iΔPβC mice. Each dot indicates a mean value of 10–20 villi/mouse and n = 5 mice/group pooled from three independent experiments. Horizontal bars indicate mean ± SD and P value versus WT by two-tailed Mann–Whitney U test. Scale bars, 50 μm. f, g Representative images and comparisons of the number of Prox1+ lymphatic endothelial cells (LECs) and Prox1+EdU+ proliferative LECs (white arrowheads) per 100 μm of lacteal length in WT and Lats1/2iΔPβC mice. Each dot indicates a mean value of 10–20 villi/mouse and n = 5 mice/group pooled from three independent experiments. Horizontal bars indicate mean ± SD and P value versus WT by two-tailed Mann–Whitney U test. Scale bars, 50 μm.