RNA Sequencing Analysis of Induced Pluripotent Stem Cell-Derived Cardiomyocytes From Congenital Heart Disease Patients

Kitani, Tomoya; Tian, Lei; Zhang, Tiejun; Itzhaki, Ilanit; Zhang, Joe Z.; Ma, Ning; Li, Chun; Rhee, June‐Wha; Romfh, Anitra; Wu, Joseph C.

doi:10.1161/circresaha.119.315653

Cited by 18 publications

(12 citation statements)

References 2 publications

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“…A recent examination of transgenic murine hearts and patient-derived iPSC-CMs study revealed the oligogenic inheritance of LVNC with the evidence for a NKX2-5 variant as a genetic modifier (187). Another recent study reported genome-wide transcriptome profiles of iPSC-CMs that were generated from patients with single ventricle heart disease and non-syndromic TOF (222). These studies provide growing evidence for the effectiveness of using iPSCs to model CHD and open the door to identifying how a modifier gene or multiple genes interact to cause CHD.…”

Section: Functional Genomics Of Chdmentioning

confidence: 99%

Genetics of congenital heart disease: a narrative review of recent advances and clinical implications

Yasuhara¹,

Garg²

2021

Transl Pediatr

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Congenital heart disease (CHD) is the most common human birth defect and remains a leading cause of mortality in childhood. Although advances in clinical management have improved the survival of children with CHD, adult survivors commonly experience cardiac and non-cardiac comorbidities, which affect quality of life and prognosis. Therefore, the elucidation of genetic etiologies of CHD not only has important clinical implications for genetic counseling of patients and families but may also impact clinical outcomes by identifying at-risk patients. Recent advancements in genetic technologies, including massively parallel sequencing, have allowed for the discovery of new genetic etiologies for CHD. Although variant prioritization and interpretation of pathogenicity remain challenges in the field of CHD genomics, advances in single-cell genomics and functional genomics using cellular and animal models of CHD have the potential to provide novel insights into the underlying mechanisms of CHD and its associated morbidities. In this review, we provide an updated summary of the established genetic contributors to CHD and discuss recent advances in our understanding of the genetic architecture of CHD along with current challenges with the interpretation of genetic variation. Furthermore, we highlight the clinical implications of genetic findings to predict and potentially improve clinical outcomes in patients with CHD.

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Section: Functional Genomics Of Chdmentioning

confidence: 99%

Genetics of congenital heart disease: a narrative review of recent advances and clinical implications

Yasuhara¹,

Garg²

2021

Transl Pediatr

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“…d-TGA is the sixth most prevalent CHD from a total of 27 anatomical subtypes, as reported in a systematic review [22]. The advent of human iPSC technologies in 2007 by Yamanaka et al [13] has been a major breakthrough for disease modeling and for therapeutic purposes [14], and detailed gene analysis of iPSC lines from patients with CHD is a promising strategy to study the mechanisms involved in the onset of cardiac diseases [23].…”

Section: Discussionmentioning

confidence: 99%

Modeling Transposition of the Great Arteries with Patient-Specific Induced Pluripotent Stem Cells

Ontoria‐Oviedo

Földes

Tejedor

et al. 2021

IJMS

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The dextro-transposition of the great arteries (d-TGA) is one of the most common congenital heart diseases. To identify biological processes that could be related to the development of d-TGA, we established induced pluripotent stem cell (iPSC) lines from two patients with d-TGA and from two healthy subjects (as controls) and differentiated them into endothelial cells (iPSC-ECs). iPSC-EC transcriptome profiling and bioinformatics analysis revealed differences in the expression level of genes involved in circulatory system and animal organ development. iPSC-ECs from patients with d-TGA showed impaired ability to develop tubular structures in an in vitro capillary-like tube formation assay, and interactome studies revealed downregulation of biological processes related to Notch signaling, circulatory system development and angiogenesis, pointing to alterations in vascular structure development. Our study provides an iPSC-based cellular model to investigate the etiology of d-TGA.

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“…The paired-end RNA-seq datasets of 10 CHDs, including 5 SVDs and 5 TOFs, and 5 healthy control samples were downloaded from the GEO database (GEO: GSE132401 ) performing on the Illumina NovaSeq 6000 platform 54 ( Table S2 ). Another paired-end RNA-seq dataset contained 3 human DCM samples and 3 control samples from the GEO database (GEO: GSE162505 ) 55 ( Table S2 ).…”

Section: Methodsmentioning

confidence: 99%

Global RNA editing identification and characterization during human pluripotent-to-cardiomyocyte differentiation

Chen

Liu

Qiao

et al. 2021

Molecular Therapy - Nucleic Acids

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RNA editing is widely involved in stem cell differentiation and development; however, RNA editing events during human cardiomyocyte differentiation have not yet been characterized and elucidated. Here, we identified genome-wide RNA editing sites and systemically characterized their genomic distribution during four stages of human cardiomyocyte differentiation. It was found that the expression level of ADAR1 affected the global number of adenosine to inosine (A-to-I) editing sites but not the editing degree. Next, we identified 43, 163, 544, and 141 RNA editing sites that contribute to changes in amino acid sequences, variation in alternative splicing, alterations in miRNA-target binding, and changes in gene expression, respectively. Generally, RNA editing showed a stage-specific pattern with 211 stage-shared editing sites. Interestingly, cardiac muscle contraction and heart-disease-related pathways were enriched by cardio-specific editing genes, emphasizing the connection between cardiomyocyte differentiation and heart diseases from the perspective of RNA editing. Finally, it was found that these RNA editing sites are also related to several congenital and noncongenital heart diseases. Together, our study provides a new perspective on cardiomyocyte differentiation and offers more opportunities to understand the mechanisms underlying cell fate determination, which can promote the development of cardiac regenerative medicine and therapies for human heart diseases.

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RNA Sequencing Analysis of Induced Pluripotent Stem Cell-Derived Cardiomyocytes From Congenital Heart Disease Patients

Cited by 18 publications

References 2 publications

Genetics of congenital heart disease: a narrative review of recent advances and clinical implications

Genetics of congenital heart disease: a narrative review of recent advances and clinical implications

Modeling Transposition of the Great Arteries with Patient-Specific Induced Pluripotent Stem Cells

Global RNA editing identification and characterization during human pluripotent-to-cardiomyocyte differentiation

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