title: Next-generation models of human cardiogenesis via genome editing.
abstract: Cardiogenesis is one of the earliest and most important steps during human development and is orchestrated by discrete families of heart progenitors, which build distinct regions of the fetal heart. For the past decade, a lineage map for the distinct subsets of progenitors that generate the embryonic mammalian heart has begun to lay a foundation for the development of new strategies for rebuilding the adult heart after injury, an unmet clinical need for the vast majority of patients with end-stage heart failure who are not heart transplant recipients. The studies also have implications for the root causes of congenital heart disease, which affects 1 in 50 live births, the most prevalent malformations in children. Although much of this insight has been generated in murine models, it is becoming increasingly clear that there can be important divergence with principles and pathways for human cardiogenesis, as well as for regenerative pathways. The development of human stem cell models, coupled with recent advances in genome editing with RNA-guided endonucleases, offers a new approach for the primary study of human cardiogenesis. In addition, application of the technology to the in vivo setting in large animal models, including nonhuman primates, has opened the door to genome-edited large animal models of adult and congenital heart disease, as well as a detailed mechanistic dissection of the more diverse and complex set of progenitor families and pathways, which guide human cardiogenesis. Implications of this new technology for a new generation of human-based, genetically tractable systems are discussed, along with potential therapeutic applications.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Solna 17177, Sweden.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Lian
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Solna 17177, Sweden.
authors.forename: Jiejia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Group of Epigenetic Reprogramming, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China School of Life Science and Technology, Shanghai Tech University, Shanghai 200031, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Solna 17177, Sweden Department of Medicine, Karolinska Institutet, Huddinge 14186, Sweden.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Chien
mesh_terms: D000818:Animals; D064113:CRISPR-Cas Systems; D002454:Cell Differentiation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D005818:Genetic Engineering / Q000379:methods; D005820:Genetic Testing; D006321:Heart / Q000196:embryology / Q000254:growth & development*; D006331:Heart Diseases / Q000628:therapy; D006801:Humans; D051379:Mice; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000637:transplantation