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<p>During development, myocardial contractile force and intracardiac hemodynamic shear stress coordinate the initiation of trabeculation. While Snail family genes are well-recognized transcription factors of epithelial-to-mesenchymal transition, <i>snai1b</i>-positive cardiomyocytes are sparsely distributed in the ventricle of zebrafish at 4 days post-fertilization. Isoproterenol treatment significantly increases the number of <i>snai1b</i>-positive cardiomyocytes, of which 80% are Notch-negative. CRISPR-activation of <i>snai1b</i> leads to 51.6% cardiomyocytes forming trabeculae, whereas CRISPR-repression reduces trabecular cardiomyocytes to 6.7% under isoproterenol. In addition, 36.7% of <i>snai1b</i>-repressed cardiomyocytes undergo apical delamination. 4-D strain analysis demonstrates that isoproterenol increases the myocardial strain along radial trabecular ridges in alignment with the <i>snai1b</i> expression and Notch-ErbB2-mediated trabeculation. Single-cell and spatial transcriptomics reveal that these <i>snai1b</i>-positive cardiomyocytes are devoid of some epithelial-to-mesenchymal transition-related phenotypes, such as Col1a2 production and induction by ErbB2 or TGF-β. Thus, we uncover <i>snai1b</i>-positive cardiomyocytes that are mechanically activated to initiate delamination for cardiac trabeculation.</p>

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Mechanically activated snai1b coordinates the initiation of myocardial delamination for trabeculation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月24日

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  • Jing Wang,
  • Aaron L. Brown,
  • Seul-Ki Park,
  • Charlie Z. Zheng,
  • Adam Langenbacher,
  • Enbo Zhu,
  • Ryan O’Donnell,
  • Peng Zhao,
  • Jeffrey J. Hsu,
  • Tomohiro Yokota,
  • Jiandong Liu,
  • Jau-Nian Chen,
  • Alison L. Marsden,
  • Tzung K. Hsiai

摘要

During development, myocardial contractile force and intracardiac hemodynamic shear stress coordinate the initiation of trabeculation. While Snail family genes are well-recognized transcription factors of epithelial-to-mesenchymal transition, snai1b-positive cardiomyocytes are sparsely distributed in the ventricle of zebrafish at 4 days post-fertilization. Isoproterenol treatment significantly increases the number of snai1b-positive cardiomyocytes, of which 80% are Notch-negative. CRISPR-activation of snai1b leads to 51.6% cardiomyocytes forming trabeculae, whereas CRISPR-repression reduces trabecular cardiomyocytes to 6.7% under isoproterenol. In addition, 36.7% of snai1b-repressed cardiomyocytes undergo apical delamination. 4-D strain analysis demonstrates that isoproterenol increases the myocardial strain along radial trabecular ridges in alignment with the snai1b expression and Notch-ErbB2-mediated trabeculation. Single-cell and spatial transcriptomics reveal that these snai1b-positive cardiomyocytes are devoid of some epithelial-to-mesenchymal transition-related phenotypes, such as Col1a2 production and induction by ErbB2 or TGF-β. Thus, we uncover snai1b-positive cardiomyocytes that are mechanically activated to initiate delamination for cardiac trabeculation.