2. Academic Validation
  3. Endothelial deletion of PTBP1 disrupts ventricular chamber development

Endothelial deletion of PTBP1 disrupts ventricular chamber development

  • Nat Commun. 2023 Mar 31;14(1):1796. doi: 10.1038/s41467-023-37409-9.
Hongyu Liu # 1 2,  Ran Duan # 1 2,  Xiaoyu He # 1 2,  Jincu Qi # 1 2,  Tianming Xing 2 3,  Yahan Wu 1 2,  Liping Zhou 1 2,  Lingling Wang 1 2,  Yujing Shao 1 2,  Fulei Zhang 1 2,  Huixing Zhou 1 2,  Xingdong Gu 2 3,  Bowen Lin 1 2,  Yuanyuan Liu 2 3,  Yan Wang 2 3,  Yi Liu 1 2,  Li Li 1 2 4 5,  Dandan Liang 6 7 8,  Yi-Han Chen 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 200120, Shanghai, China.
  • 2 Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, 200120, Shanghai, China.
  • 3 Jinzhou Medical University, 121000, Jinzhou, Liaoning, China.
  • 4 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, 200092, Shanghai, China.
  • 5 Department of Pathology and Pathophysiology, Tongji University School of Medicine, 200092, Shanghai, China.
  • 6 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 200120, Shanghai, China. dandanliang@tongji.edu.cn.
  • 7 Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, 200120, Shanghai, China. dandanliang@tongji.edu.cn.
  • 8 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, 200092, Shanghai, China. dandanliang@tongji.edu.cn.
  • 9 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, 200120, Shanghai, China. yihanchen@tongji.edu.cn.
  • 10 Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, 200120, Shanghai, China. yihanchen@tongji.edu.cn.
  • 11 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, 200092, Shanghai, China. yihanchen@tongji.edu.cn.
  • 12 Department of Pathology and Pathophysiology, Tongji University School of Medicine, 200092, Shanghai, China. yihanchen@tongji.edu.cn.
  • # Contributed equally.
PMID: 37002228 DOI: 10.1038/s41467-023-37409-9
Abstract

The growth and maturation of the ventricular chamber require spatiotemporally precise synergy between diverse cell types. Alternative splicing deeply affects the processes. However, the functional properties of alternative splicing in cardiac development are largely unknown. Our study reveals that an alternative splicing factor polypyrimidine tract-binding protein 1 (PTBP1) plays a key role in ventricular chamber morphogenesis. During heart development, PTBP1 colocalizes with endothelial cells but is almost undetectable in cardiomyocytes. The endothelial-specific knockout of Ptbp1, in either endocardial cells or pan-endothelial cells, leads to a typical phenotype of left ventricular noncompaction (LVNC). Mechanistically, the deletion of Ptbp1 reduces the migration of endothelial cells, disrupting cardiomyocyte proliferation and ultimately leading to the LVNC. Further study shows that Ptbp1 deficiency changes the alternative splicing of β-arrestin-1 (Arrb1), which affects endothelial cell migration. In conclusion, as an alternative splicing factor, PTBP1 is essential during ventricular chamber development, and its deficiency can lead to congenital heart disease.

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