Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

Gun Sik Cho, Dong I. Lee, Emmanouil Tampakakis, Sean Murphy, Peter Andersen, Hideki Uosaki, Stephen Chelko, Khalid Chakir, Ingie Hong, Kinya Seo, Huei Sheng Vincent Chen, Xiongwen Chen, Cristina Basso, Steven R. Houser, Gordon F. Tomaselli, Brian O'Rourke, Daniel P. Judge, David A. Kass, Chulan Kwon

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

Original languageEnglish (US)
Pages (from-to)571-582
Number of pages12
JournalCell Reports
Volume18
Issue number2
DOIs
StatePublished - Jan 10 2017
Externally publishedYes

Fingerprint

Pluripotent Stem Cells
Stem cells
Cardiomyopathies
Cardiac Myocytes
Transplantation
Arrhythmogenic Right Ventricular Dysplasia
RNA Sequence Analysis
Rats
Heart Diseases
RNA
Phenotype

Keywords

  • ARVC
  • calcium transient
  • cardiac progenitor
  • cardiomyocyte
  • cardiomyopathy
  • disease modeling
  • iPS
  • maturation
  • neonatal
  • sarcomere shortening
  • T-tubule

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cho, G. S., Lee, D. I., Tampakakis, E., Murphy, S., Andersen, P., Uosaki, H., ... Kwon, C. (2017). Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy. Cell Reports, 18(2), 571-582. https://doi.org/10.1016/j.celrep.2016.12.040

Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy. / Cho, Gun Sik; Lee, Dong I.; Tampakakis, Emmanouil; Murphy, Sean; Andersen, Peter; Uosaki, Hideki; Chelko, Stephen; Chakir, Khalid; Hong, Ingie; Seo, Kinya; Chen, Huei Sheng Vincent; Chen, Xiongwen; Basso, Cristina; Houser, Steven R.; Tomaselli, Gordon F.; O'Rourke, Brian; Judge, Daniel P.; Kass, David A.; Kwon, Chulan.

In: Cell Reports, Vol. 18, No. 2, 10.01.2017, p. 571-582.

Research output: Contribution to journalArticle

Cho, GS, Lee, DI, Tampakakis, E, Murphy, S, Andersen, P, Uosaki, H, Chelko, S, Chakir, K, Hong, I, Seo, K, Chen, HSV, Chen, X, Basso, C, Houser, SR, Tomaselli, GF, O'Rourke, B, Judge, DP, Kass, DA & Kwon, C 2017, 'Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy', Cell Reports, vol. 18, no. 2, pp. 571-582. https://doi.org/10.1016/j.celrep.2016.12.040
Cho, Gun Sik ; Lee, Dong I. ; Tampakakis, Emmanouil ; Murphy, Sean ; Andersen, Peter ; Uosaki, Hideki ; Chelko, Stephen ; Chakir, Khalid ; Hong, Ingie ; Seo, Kinya ; Chen, Huei Sheng Vincent ; Chen, Xiongwen ; Basso, Cristina ; Houser, Steven R. ; Tomaselli, Gordon F. ; O'Rourke, Brian ; Judge, Daniel P. ; Kass, David A. ; Kwon, Chulan. / Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy. In: Cell Reports. 2017 ; Vol. 18, No. 2. pp. 571-582.
@article{896796e3bd894a15b45496d3e2925dfc,
title = "Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy",
abstract = "Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.",
keywords = "ARVC, calcium transient, cardiac progenitor, cardiomyocyte, cardiomyopathy, disease modeling, iPS, maturation, neonatal, sarcomere shortening, T-tubule",
author = "Cho, {Gun Sik} and Lee, {Dong I.} and Emmanouil Tampakakis and Sean Murphy and Peter Andersen and Hideki Uosaki and Stephen Chelko and Khalid Chakir and Ingie Hong and Kinya Seo and Chen, {Huei Sheng Vincent} and Xiongwen Chen and Cristina Basso and Houser, {Steven R.} and Tomaselli, {Gordon F.} and Brian O'Rourke and Judge, {Daniel P.} and Kass, {David A.} and Chulan Kwon",
year = "2017",
month = "1",
day = "10",
doi = "10.1016/j.celrep.2016.12.040",
language = "English (US)",
volume = "18",
pages = "571--582",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Neonatal Transplantation Confers Maturation of PSC-Derived Cardiomyocytes Conducive to Modeling Cardiomyopathy

AU - Cho, Gun Sik

AU - Lee, Dong I.

AU - Tampakakis, Emmanouil

AU - Murphy, Sean

AU - Andersen, Peter

AU - Uosaki, Hideki

AU - Chelko, Stephen

AU - Chakir, Khalid

AU - Hong, Ingie

AU - Seo, Kinya

AU - Chen, Huei Sheng Vincent

AU - Chen, Xiongwen

AU - Basso, Cristina

AU - Houser, Steven R.

AU - Tomaselli, Gordon F.

AU - O'Rourke, Brian

AU - Judge, Daniel P.

AU - Kass, David A.

AU - Kwon, Chulan

PY - 2017/1/10

Y1 - 2017/1/10

N2 - Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

AB - Pluripotent stem cells (PSCs) offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs). Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases.

KW - ARVC

KW - calcium transient

KW - cardiac progenitor

KW - cardiomyocyte

KW - cardiomyopathy

KW - disease modeling

KW - iPS

KW - maturation

KW - neonatal

KW - sarcomere shortening

KW - T-tubule

UR - http://www.scopus.com/inward/record.url?scp=85009186327&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009186327&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.12.040

DO - 10.1016/j.celrep.2016.12.040

M3 - Article

C2 - 28076798

AN - SCOPUS:85009186327

VL - 18

SP - 571

EP - 582

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 2

ER -