Fig. 1

Mesenchymal-to-epithelial transition in hearts after apical resection. a Schematic diagram illustrating the approach used to generate Ck19-CreER mice. b Immunostaining for tdTomato and PDGFRa or CD31 on hearts of Ck19-CreER;Ai9 mice, which received tamoxifen treatment at E17.5 and harvested for analysis at P1. The arrows indicate the tdTomato-labeled epicardium. The triangles indicate the tdTomato-labeled endothelial cells. Insets indicate colocalization of tdTomato with PDGFRa or CD31. c, d Immunostaining for tdTomato and CK19 on P22 hearts of Ck19-CreER;Ai9 mice, which were treated with tamoxifen at E17.5 and subjected to AR at P1. The open arrows in d indicate tdTomato^– epicardial cells in the apex. e The percentage of tdTomato-labeled epicardial cells (tdTomato⁺CK19⁺DAPI⁺/CK19⁺DAPI⁺) in the base and apex at P22 following injury. The data are represented as mean values ± SEM and were analyzed using an unpaired Student’s t-test. n = 6 mice per group. ***p < 0.001. Significance was accepted when p < 0.05. f The strategy for generating Fap-CreER mice. g tdTomato expression in the sham- or AR-operated hearts of Fap-CreER;Ai9 mice at P8. The mice were subjected to AR at P1 and treated with tamoxifen at P6. h–j Immunostaining for tdTomato and PDGFRa, WT1 or CK19 on hearts of Fap-CreER;Ai9 mice at P8. The yellow arrows in h indicate tdTomato-labeled fibroblasts. The open arrows in i and j indicate tdTomato^– epicardial cells. k, l Immunostaining for tdTomato and WT1 or CK19 on hearts of Fap-CreER;Ai9 mice at P22. The white arrows in k and l indicate tdTomato-labeled epicardial cells. White scale bars, 100 µm; Yellow scale bars, 500 µm; Red scale bars, 50 µm. 3′ UTR, 3′ untranslated region; Wpre, woodchuck hepatitis virus posttranscriptional regulatory element; poly A, polyadenylation; AR, apical resection; DAPI, 4′, 6-diamidino-2-phenylindole. E, embryonic day; P, postnatal day. Each picture in b and g–i is representative of 5 individual samples. Each picture in c and d is representative of 6 individual samples