Faculty Collaboration Database

Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells. Cardiovasc Res 2014 Nov 01;104(2):258-69

Date

09/12/2014

Pubmed ID

25209314

Pubmed Central ID

PMC4217687

DOI

10.1093/cvr/cvu205

Scopus ID

2-s2.0-84913590117 (requires institutional sign-in at Scopus site)   141 Citations

Abstract

AIMS: Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies.

METHODS AND RESULTS: To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for 'Cell Proliferation' was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments.

CONCLUSION: Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases.

Author List

Han L, Li Y, Tchao J, Kaplan AD, Lin B, Li Y, Mich-Basso J, Lis A, Hassan N, London B, Bett GC, Tobita K, Rasmusson RL, Yang L

Author

Lu Han PhD Assistant Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Adult
Animals
Calcium Signaling
Cardiac Myosins
Cardiomyopathy, Hypertrophic, Familial
Case-Control Studies
Cell Proliferation
Cell Separation
Cells, Cultured
Cellular Reprogramming
Cellular Reprogramming Techniques
Female
Gene Expression Profiling
Gene Expression Regulation
Gene Regulatory Networks
Genetic Predisposition to Disease
Humans
Induced Pluripotent Stem Cells
Mice, Inbred NOD
Mice, SCID
Myocytes, Cardiac
Myosin Heavy Chains
Phenotype
Sarcomeres
Transcriptome