Fig. 6: Loss-of-MYH10 phenocopies LIPTER deficiency in CMs.

a, CRISPR/Cas-9-mediated deletion of MYH10 exon 1 in hiPSCs. b, RT–qPCR detection of MYH10 expressions in WT and MYH10^KO hiPSC-CMs (n = 3 independent experiments). c, Representative images of Oil Red O staining and cTnT immunostaining (first two columns), and Nile Red for LDs and cTnT co-staining (third column) on MYH10^KO and WT hiPSC-EB sections. d, Quantification of Oil Red O⁺ areas in cTnT⁺ areas in c (n = 3 independent experiments). e, TEM showing mitochondrial morphologies in WT and MYH10^KO hiPSC-CMs. Normal (green arrows) and swollen (red arrowheads) mitochondria indicated. f, Quantification of swollen mitochondria ratios in e (n = 3 independent experiments). g,h, Statistical results of maximum respiratory capacity and spare respiratory capacity (n = 3 independent experiments) (g), and FAO capacities (n = 3 independent experiments) in WT and MYH10^KO hiPSC-CMs (h). i, Quantification of TUNEL⁺ CMs ratios in MYH10^KO and WT hiPSC-EBs (n = 3 independent experiments). j, Scheme of inhibiting MYH10 function in LIPTER-overexpressing hiPSC-CMs. k, Representative images of Oil Red O staining and cTnT immunostaining in LIPTER^KO/OE hiPSC-CMs after treatment with (S)-(−)-Blebbistatin ((S)-BB) or control (R)-(−)-Blebbistatin ((R)-BB) for 10 days. l, Ratios of Oil Red O⁺ areas in cTnT⁺ CM areas in k (n = 4 independent experiments). m, FAO capacities of LIPTER^KO/OE hiPSC-CMs after treating with (S)-BB or (R)-BB for 10 days (n = 3 independent experiments). n, Ratios of TUNEL⁺ CM in LIPTER^KO/OE hiPSC-CMs after same treatment in m (n = 3 independent experiments). o, Scheme for HFD feeding of mice with conditional Myh10 knockout in CMs. p, RT–qPCR detecting Myh10 expression levels in mouse hearts. q–s, Representative images of Oil Red O lipid staining of mouse hearts (q), and quantifications of TAG (r) and FA (s) concentrations in mouse hearts after 3 months of HFD feeding (n = 4 mice). t, FAO rates of whole Myh10^f/f and Myh10^CKO mouse hearts post HDF feeding (n = 5 mice). u,v, Cardiac EF (u) and FS (v) measurements of Myh10^f/f and Myh10^CKO mice post HFD feeding (n = 4 mice). In b, f, d–i, l–n and r–v, bars are presented as mean ± s.e.m. Unpaired two-tailed t-test is used for comparison. Source numerical data are available in source data.

Source data