Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs)
Congenital heart disease (CHD) is the most common cause of infant death associated with birth defects. Recent next-generation genome sequencing has uncovered novel genetic etiologies of CHD, from inherited and de novo variants to non-coding genetic variants. The next phase of understanding the genet...
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doaj-d3db26e4659b4fae8c4452ce5132c96e2021-01-21T08:53:26ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-01-01910.3389/fcell.2021.630069630069Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs)Hui Lin0Hui Lin1Hui Lin2Kim L. McBride3Kim L. McBride4Kim L. McBride5Kim L. McBride6Vidu Garg7Vidu Garg8Vidu Garg9Vidu Garg10Ming-Tao Zhao11Ming-Tao Zhao12Ming-Tao Zhao13Center for Cardiovascular Research, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, United StatesThe Heart Center, Nationwide Children’s Hospital, Columbus, OH, United StatesDivision of Genetic and Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, United StatesCenter for Cardiovascular Research, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, United StatesThe Heart Center, Nationwide Children’s Hospital, Columbus, OH, United StatesDivision of Genetic and Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, United StatesDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United StatesCenter for Cardiovascular Research, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, United StatesThe Heart Center, Nationwide Children’s Hospital, Columbus, OH, United StatesDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United StatesDepartment of Molecular Genetics, The Ohio State University, Columbus, OH, United StatesCenter for Cardiovascular Research, The Abigail Wexner Research Institute, Nationwide Children’s Hospital, Columbus, OH, United StatesThe Heart Center, Nationwide Children’s Hospital, Columbus, OH, United StatesDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, United StatesCongenital heart disease (CHD) is the most common cause of infant death associated with birth defects. Recent next-generation genome sequencing has uncovered novel genetic etiologies of CHD, from inherited and de novo variants to non-coding genetic variants. The next phase of understanding the genetic contributors of CHD will be the functional illustration and validation of this genome sequencing data in cellular and animal model systems. Human induced pluripotent stem cells (iPSCs) have opened up new horizons to investigate genetic mechanisms of CHD using clinically relevant and patient-specific cardiac cells such as cardiomyocytes, endothelial/endocardial cells, cardiac fibroblasts and vascular smooth muscle cells. Using cutting-edge CRISPR/Cas9 genome editing tools, a given genetic variant can be corrected in diseased iPSCs and introduced to healthy iPSCs to define the pathogenicity of the variant and molecular basis of CHD. In this review, we discuss the recent progress in genetics of CHD deciphered by large-scale genome sequencing and explore how genome-edited patient iPSCs are poised to decode the genetic etiologies of CHD by coupling with single-cell genomics and organoid technologies.https://www.frontiersin.org/articles/10.3389/fcell.2021.630069/fullcongenital heart diseasehuman induced pluripotent stem cellsNOTCH signalinghypoplastic left heart syndromegenetic models of CHD |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hui Lin Hui Lin Hui Lin Kim L. McBride Kim L. McBride Kim L. McBride Kim L. McBride Vidu Garg Vidu Garg Vidu Garg Vidu Garg Ming-Tao Zhao Ming-Tao Zhao Ming-Tao Zhao |
spellingShingle |
Hui Lin Hui Lin Hui Lin Kim L. McBride Kim L. McBride Kim L. McBride Kim L. McBride Vidu Garg Vidu Garg Vidu Garg Vidu Garg Ming-Tao Zhao Ming-Tao Zhao Ming-Tao Zhao Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs) Frontiers in Cell and Developmental Biology congenital heart disease human induced pluripotent stem cells NOTCH signaling hypoplastic left heart syndrome genetic models of CHD |
author_facet |
Hui Lin Hui Lin Hui Lin Kim L. McBride Kim L. McBride Kim L. McBride Kim L. McBride Vidu Garg Vidu Garg Vidu Garg Vidu Garg Ming-Tao Zhao Ming-Tao Zhao Ming-Tao Zhao |
author_sort |
Hui Lin |
title |
Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs) |
title_short |
Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs) |
title_full |
Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs) |
title_fullStr |
Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs) |
title_full_unstemmed |
Decoding Genetics of Congenital Heart Disease Using Patient-Derived Induced Pluripotent Stem Cells (iPSCs) |
title_sort |
decoding genetics of congenital heart disease using patient-derived induced pluripotent stem cells (ipscs) |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-01-01 |
description |
Congenital heart disease (CHD) is the most common cause of infant death associated with birth defects. Recent next-generation genome sequencing has uncovered novel genetic etiologies of CHD, from inherited and de novo variants to non-coding genetic variants. The next phase of understanding the genetic contributors of CHD will be the functional illustration and validation of this genome sequencing data in cellular and animal model systems. Human induced pluripotent stem cells (iPSCs) have opened up new horizons to investigate genetic mechanisms of CHD using clinically relevant and patient-specific cardiac cells such as cardiomyocytes, endothelial/endocardial cells, cardiac fibroblasts and vascular smooth muscle cells. Using cutting-edge CRISPR/Cas9 genome editing tools, a given genetic variant can be corrected in diseased iPSCs and introduced to healthy iPSCs to define the pathogenicity of the variant and molecular basis of CHD. In this review, we discuss the recent progress in genetics of CHD deciphered by large-scale genome sequencing and explore how genome-edited patient iPSCs are poised to decode the genetic etiologies of CHD by coupling with single-cell genomics and organoid technologies. |
topic |
congenital heart disease human induced pluripotent stem cells NOTCH signaling hypoplastic left heart syndrome genetic models of CHD |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.630069/full |
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