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| Open AccessPlacental growth factor exerts a dual function for cardiomyogenesis and vasculogenesis during heart development
Growth factors play key roles during heart development. Here they show that PLGF has both autocrine and paracrine roles during cardiomyogenesis and vasculogenesis, suggesting it may have therapeutic potential for heart disease.
- Nevin Witman
- , Chikai Zhou
- & Makoto Sahara
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Article
| Open AccessActivation of Nkx2.5 transcriptional program is required for adult myocardial repair
Cardiac developmental genes have been associated with regenerative potential. Here the authors identify a Nkx2.5-dependent gene regulatory network operating through ect2, psmb3, and psmd7 to orchestrate cell cycle re-entry, proteolysis, and mitochondrial metabolism during myocardial repair.
- Carmen de Sena-Tomás
- , Angelika G. Aleman
- & Kimara L. Targoff
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| Open AccessMassively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation
Throughput of in vivo genetic screens is a barrier to efficient application. Here the authors use a high-throughput CRISPR-based in vivo forward genetic screen in mice to identify transcriptional regulators of cardiomyocyte maturation, including the epigenetic modifiers RNF20 and RNF40.
- Nathan J. VanDusen
- , Julianna Y. Lee
- & William T. Pu
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| Open AccessERRγ enhances cardiac maturation with T-tubule formation in human iPSC-derived cardiomyocytes
Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) suffer from limited maturation. Here the authors identify ERRγ agonist as a factor that enhances cardiac morphological, metabolic, contractile and electrical maturation of hiPSC-derived CMs with T-tubule formation.
- Kenji Miki
- , Kohei Deguchi
- & Yoshinori Yoshida
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| Open AccessGeneration of mature compact ventricular cardiomyocytes from human pluripotent stem cells
Cardiomyocytes of heart ventricles consist of subpopulations of trabecular and compact subtypes. Here the authors describe the generation of structurally, metabolically and functionally mature compact ventricular cardiomyocytes as well as mature atrial cardiomyocytes from human pluripotent stem cells.
- Shunsuke Funakoshi
- , Ian Fernandes
- & Gordon Keller
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| Open AccessPGC1/PPAR drive cardiomyocyte maturation at single cell level via YAP1 and SF3B2
Cardiomyocyte maturation and the acquisition of phenotypes is poorly understood at the single cell level. Here, the authors analyse the transcriptome of single cells from neonatal to adult heart and reveal that peroxisome proliferator-activated receptor coactivator-1 mediates the phenotypic shift.
- Sean A. Murphy
- , Matthew Miyamoto
- & Chulan Kwon
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Article
| Open AccessFunctional cardiac fibroblasts derived from human pluripotent stem cells via second heart field progenitors
Cardiac fibroblasts (CFs) play critical roles in heart development, homeostasis, and disease. Here the authors efficiently differentiate human pluripotent stem cells through second heart field progenitors to CFs that exhibit features and functional properties similar to native CFs.
- Jianhua Zhang
- , Ran Tao
- & Timothy J. Kamp
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| Open AccessBRG1-SWI/SNF-dependent regulation of the Wt1 transcriptional landscape mediates epicardial activity during heart development and disease
Priming of the adult mouse heart with Tβ4 activates dormant epicardium-derived cells to aid repair of injured myocardium. Here, Vieiraet al. explain this process and show that Tβ4 binds a chromatin remodeller BRG1 and activates Wt1, the key regulator of epicardial epithelial-to-mesenchymal transformation, by altering the epigenetic landscape of the Wt1 locus.
- Joaquim Miguel Vieira
- , Sara Howard
- & Paul R. Riley
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| Open AccessTherapeutic microparticles functionalized with biomimetic cardiac stem cell membranes and secretome
Stem cells exert their beneficial effects through secretion of regenerative factors. Here, the authors take the membranes and secreted factors from cardiac stem cells and generate a synthetic cell-mimicking microparticle, which, on injection in a mouse model of myocardial infarction, improves cardiac function.
- Junnan Tang
- , Deliang Shen
- & Ke Cheng