LRRC10 regulates mammalian cardiomyocyte cell cycle during heart regeneration

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  Fig. 1. Cardiac regeneration is inhibited in the neonatal Lrrc10–/– mouse with disruption of the transcriptional landscape following injury. Control and Lrrc10–/– neonatal mice underwent a sham (SH) or myocardial infarction (MI) surgery at P1 and were analyzed at 7-, 14-, or 21 days post-surgery (DPS). a Mason’s trichrome staining (viable tissue in red; scar tissue in blue) at 21DPS (n = 5); scale bar =1 mm. b Analysis of Heart Weight to Body Weight (BW) ratio (n = 12). c Analysis of cardiomyocyte mitosis with pH3 and cTnT at 7DPS (n = 7); scale bar =10uM. d Analysis of cytokinesis by symmetrical localization of Aurora B with cTnT at 7DPS (SH n = 3; MI n = 7); arrowhead indicates Aurora B localization between cardiomyocytes; scale bar =10uM. e Percentage of mononucleated (Mono), binucleated (Bi), and multinucleated (Multi) cardiomyocytes per heart at 14DPS (WT n = 4; KO n = 5); scale bar =20uM. f Quantification of cardiomyocyte size by Wheat Germ Agglutinin (WGA) at 21DPS (n = 5); scale bar =25uM. Hearts were collected from WT and Lrrc10–/– mice at 7 days after sham or MI surgery, processed for bulk-tissue RNA-sequencing (n = 4 per group), and the transcriptome of differentially…

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  Fig. 2. LRRC10 overexpression rescues heart regeneration in Lrrc10–/– mice. a Control and Lrrc10–/– neonatal mice were treated with a single-dose of AAV9-cTnT-GFP control or AAV9-cTnT-LRRC10 rescue viral vector before undergoing sham or MI surgery at P1. b Efficient transfection shown by GFP expression in WT P8 mice treated with or without AAV9-cTnT-GFP at P0 (n = 3). Hearts were analyzed for regeneration hallmarks at 7-, 14- and 28-days post-MI (DPMI). c Cytokinesis measured by symmetrical Aurora B within cardiomyocytes, marked by cTnT at 7DPMI (n = 4). d Nucleation percentages of mononucleated (Mono), binucleated (Bi), and multinucleated (Multi) cardiomyocytes (WT and KO controls n = 9; KO rescue n = 8) at 14DPMI. e Masson’s trichrome analysis at 28DPMI (n = 4); scale bar =1 mm. f Heart weight to body weight (BW) ratios at 28DPMI (WT control n = 9; KO control n = 8; KO rescue n = 6). g Echocardiography of ejection fraction (EF) and fractional shortening (FS) at 28DPMI (WT control n = 9; KO control n = 8; KO rescue n = 6). *P \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs}…