Mechanically Activated snai1b Coordinates the Initiation of Myocardial Delamination for Trabeculation

Authors

  • Jing Wang University of California, Los Angeles, Los Angeles, USA
  • Aaron L Brown Stanford University, Stanford, USA
  • Seul-Ki Park University of California, Los Angeles, Los Angeles, USA
  • Charlie Z Zheng University of California, Los Angeles, Los Angeles, USA
  • Adam Langenbacher University of California, Los Angeles, Los Angeles, USA
  • Enbo Zhu University of California, Los Angeles, Los Angeles, USA
  • Ryan O'Donnell University of California, Los Angeles, Los Angeles, USA
  • Peng Zhao University of California, Los Angeles, Los Angeles, USA
  • Jeffrey Hsu University of California, Los Angeles, Los Angeles, USA
  • Jiandong Liu University of North Carolina at Chapel Hill, Chapel Hill, USA
  • Jau-Nian Chen University of California, Los Angeles, Los Angeles, USA
  • Tomohiro Yokota University of California, Los Angeles, Los Angeles, USA and Greater Los Angeles VA Healthcare System, Los Angeles, USA
  • Alison L Marsden Stanford University, Stanford, USA
  • Tzung K Hsiai University of California, Los Angeles, Los Angeles, USA and Greater Los Angeles VA Healthcare System, Los Angeles, USA

DOI:

https://doi.org/10.21542/gcsp.2025.hvbte.22

Abstract

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 (EMT), snai1b-positive (+) cardiomyocytes (CMs) are sparsely distributed in the ventricle of zebrafish at 4 days post-fertilization (dpf). Isoproterenol (ISO) treatment significantly increased the number of snai1b+ CMs, of which 80% were Notch-negative. CRISPR-activation of snai1b led to 51.6% CMs forming trabeculae, whereas CRISPR-repression reduced trabecular CMs to 6.7% under ISO. In addition, 36.7% of snai1b-repressed CMs underwent apical delamination. 4-D strain analysis demonstrated that ISO increased the myocardial strain along radial trabecular ridges in alignment with the snai1b expression and Notch-ErbB2-mediated trabeculation. Single-cell and spatial transcriptomics revealed that these snai1b+ CMs were devoid of some EMT-related phenotypes, such as collagen 1a2 production and induction by ErbB2 or TGF-b. Thus, we uncovered snai1b+ CMs that are mechanically activated to initiate delamination for cardiac trabeculation.

Published

2025-10-06

Issue

Vol. 2025 No. HVBTE (2025): Proceedings of the The 10th Heart Valve Biology and Tissue Engineering Meeting

Section

Mechanobiology

License

Copyright (c) 2025 Jing Wang, Aaron L Brown, Seul-Ki Park, Charlie Z Zheng, Adam Langenbacher, Enbo Zhu, Ryan O'Donnell, Peng Zhao, Jeffrey Hsu, Jiandong Liu, Jau-Nian Chen, Tomohiro Yokota, Alison L Marsden, Tzung K Hsiai

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.