Next-generation models of human cardiogenesis via genome editing

Xiaojun Lian, Jiejia Xu, Jinsong Li, Kenneth R. Chien

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
JournalCold Spring Harbor perspectives in medicine
Volume4
Issue number12
DOIs
StatePublished - Jan 1 2014

Fingerprint

Genes
Human Development
Heart Diseases
Animal Models
Heart Injuries
Technology
Fetal Heart
Endonucleases
Live Birth
Primates
Dissection
Animals
Stem Cells
Heart Failure
Genome
RNA
Transplants
Gene Editing
Stem cells
Therapeutics

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lian, Xiaojun ; Xu, Jiejia ; Li, Jinsong ; Chien, Kenneth R. / Next-generation models of human cardiogenesis via genome editing. In: Cold Spring Harbor perspectives in medicine. 2014 ; Vol. 4, No. 12.
@article{e496bfb4464d4ff6a8bde305af79e2aa,
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.",
author = "Xiaojun Lian and Jiejia Xu and Jinsong Li and Chien, {Kenneth R.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1101/cshperspect.a013920",
language = "English (US)",
volume = "4",
journal = "Cold Spring Harbor perspectives in medicine",
issn = "2157-1422",
publisher = "Cold Spring Harbor Laboratory Press",
number = "12",

}

Next-generation models of human cardiogenesis via genome editing. / Lian, Xiaojun; Xu, Jiejia; Li, Jinsong; Chien, Kenneth R.

In: Cold Spring Harbor perspectives in medicine, Vol. 4, No. 12, 01.01.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Next-generation models of human cardiogenesis via genome editing

AU - Lian, Xiaojun

AU - Xu, Jiejia

AU - Li, Jinsong

AU - Chien, Kenneth R.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84923879860&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923879860&partnerID=8YFLogxK

U2 - 10.1101/cshperspect.a013920

DO - 10.1101/cshperspect.a013920

M3 - Article

VL - 4

JO - Cold Spring Harbor perspectives in medicine

JF - Cold Spring Harbor perspectives in medicine

SN - 2157-1422

IS - 12

ER -