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Single-Cell Transcriptomics of Engineered Cardiac Tissues from Patient-Specific Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals Abnormal Developmental Trajectory and Intrinsic Contractile Defects in Hypoplastic Right Heart Syndrome

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干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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http://data.iscr.ac.cn/Article?id=f19ff8a54cea99635cd85dc04d4b934a
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Pulmonary atresia with intact ventricular septum (PAIVS) is a subset of hypoplastic right heart syndrome, a form of congenital heart disease (CHD). Genomic studies on PAIVS patients revealed inconclusive genomic variations and polymorphisms and no animal model yet exists for this disease. Hence, we performed single cell RNA-sequencing (scRNA-seq) on PAIVS patient derived human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) and its bioengineered cardiac tissue constructs (Human cardiac anisotropic sheeet (hCAS) and cardiac tissue strip (hCTS)) to dissect the intrinsic cardiomyocyte defects. Using pseudotime analysis, we identified pro-maturational cues conferred to hiPSC-CMs by hCAS and hCTS and are attenduated in PAIVS. Moerover, we also identified diminished expression of cardiac contractile apparatus genes in PAIVS hiPSC-CMs and hCTS. Our findings reveal intrinsic abnormalities in cardiac contraction and development in PAIVS in the absence of secondary in vivo remodelling.
提供机构:
The University of Hong Kong
创建时间:
2022-02-20
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