Fig. 6: Proliferation of cardiomyocytes and Müller cells.

a A protein immunoblot indicates that TRULI decreases the phosphorylation of Yap in neonatal cardiomyocytes in vitro. b Quantification of the data in panel a shows the significance of the effect (p = 0.008 by an unpaired, two-tailed t-test, n = 4 independent biological samples, mean ± SEM). c Immunofluorescent labeling discloses that 3 days of TRULI treatment elevates the cell-cycle marker Ki67 (arrowheads) in cardiomyocytes. Scale bars, 100 μm. d Quantification again reveals significant effects for Ki67 (p = 0.001 by an unpaired, two-tailed t-test, n = 4, mean ± SEM). e A marker of mitotic initiation, pH3, is similarly elevated by treatment (p = 0.026 by an unpaired, two-tailed t-test, n = 4, mean ± SEM). f The cardiomyocyte solidity, an index of cellular shape, decreases significantly after treatment, an effect consistent with de-differentiation (p = 1.09 × 10⁻⁴⁰, by an unpaired, two-tailed t-test, n = 232 control cells and 197 TRULI-treated cells, mean ± SEM). g TRULI treatment reduces the areas of cardiomyocytes, another sign of mitosis (p = 4.09 × 10⁻¹³ by an unpaired, two-tailed t-test, n = 231 control cells and 197 TRULI-treated cells, mean ± SEM). h A protein immunoblot indicates that 24 h of treatment with TRULI decreases the phosphorylation of Yap in Sox9-marked Müller cells of human retinal organoids. i A bar graph documents the effect observed in panel h (p = 0.024 by an unpaired, two-tailed t-test, n = 3, mean ± SEM). j After 5 days of TRULI treatment, EdU labeling shows a substantial increase in cellular proliferation. k A bar graph quantifies the result of panel j in three experiments (p = 2.35 × 10⁻¹³ by an unpaired, two-tailed t-test, n = 15 control organoids and 16 TRULI-treated organoids, mean ± SEM).