Goh, Q; Song, T; Petrany, MJ; Cramer, AA W; Sun, C; Sadayappan, S; Lee, S; Millay, DP. Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle. eLife. 2019; 8.
In this paper we showed that skeletal muscle adapts to exercise by adding new nuclei from stem cells. Without an ability to add new nuclei, muscle is unable to repair damage or grow larger in size.
Hulin, A; Hortells, L; Gomez-Stallons, MV; O'Donnell, A; Chetal, K; Adam, M; Lancellotti, P; Oury, C; Potter, SS; Salomonis, N; Yutzey, KE. Maturation of heart valve cell populations during postnatal remodeling. Development (Cambridge). 2019; 146(12).
Single cell RNA sequencing was used to identify novel cell populations and surprising endothelial and interstitial cell diversity in postnatal mouse heart valves. This transcriptomic analysis of postnatal heart valves at single cell resolution demonstrates that subpopulations of endothelial and immune cells are relatively constant throughout postnatal development, but interstitial cell subpopulations undergo changes in gene expression and cellular functions in primordial and mature valves.
Meng, Q; Bhandary, B; Bhuiyan, MS; James, J; Osinska, H; Valiente-Alandi, I; Shay-Winkler, K; Gulick, J; Molkentin, JD; Blaxall, BC; Robbins, J. Myofibroblast-Specific TGF beta Receptor II Signaling in the Fibrotic Response to Cardiac Myosin Binding Protein C-Induced Cardiomyopathy. Circulation Research. 2018; 123(12):1285-1297.
Using a chronic, genetically induced model of cardiac disease and fibrosis induced by cardiomyocyte-specific expression of a cardiac myosin binding protein C fragment, we ablated TGFβ signaling only in the myofibroblasts and showed that TGFβ signaling in that cell type is necessary for fibrosis to occur. By inducing and then later ablating myofibroblast-based, TGFβ signaling after fibrosis was established, we demonstrated that TGFβ signaling is required for myofibroblast and fibrotic maintenance, as fibrosis could be partially reversed if TGFβ signaling was stopped after extensive fibrosis had occurred.
Schips, TG; Vanhoutte, D; Vo, A; Correll, RN; Brody, MJ; Khalil, H; Karch, J; Tjondrokoesoemo, A; Sargent, MA; Maillet, M; Ross, RS; Molkentin, JD. Thrombospondin-3 augments injury-induced cardiomyopathy by intracellular integrin inhibition and sarcolemmal instability. Nature Communications. 2019; 10(1).
Here we showed that the gene thrombospondin-3 (Thbs3), when induced in the mouse heart after injury, causes destabilization of the plasma membrane, making disease stimuli more severe. Indeed, mice with this gene deleted are protected from cardiomyopathy following pressure overload or excessive β-adrenegric stimulation.
Song, YC; Dohn, TE; Rydeen, AB; Nechiporuk, AV; Waxman, JS. HDAC1-mediated repression of the retinoic acid-responsive gene ripply3 promotes second heart field development. PLoS genetics. 2019; 15(5).
Here we showed using zebrafish mutants that the epigenetic modifier histone deacetylase 1 (HDAC1) is critical for promoting proliferation of later-differentiating cardiac progenitor cells. Furthermore, we found that enhanced expression of ripply3, which is responsive to retinoic acid and implicated in congenital heart defects of children with Down syndrome, is a key effector of the cardiac defects in zebrafish hdac1 mutants.