An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors
Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by...
Saved in:
Published in | PloS one Vol. 6; no. 1; p. e16004 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
04.01.2011
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 Conceived and designed the experiments: CR SSYW FWK SSM WL DJE RJL HSB. Performed the experiments: CR SSYW FWK SSM WL HSB. Analyzed the data: CR SSYW SSM WL DJE RJL HSB. Contributed reagents/materials/analysis tools: DJE RJL HSB. Wrote the paper: CR SSYW HSB. Obtained permission for use of cell line: RJL. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0016004 |