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...

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Main Authors: Carissa Ritner, Sharon S Y Wong, Frank W King, Shirley S Mihardja, Walter Liszewski, David J Erle, Randall J Lee, Harold S Bernstein
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3014940?pdf=render
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author Carissa Ritner
Sharon S Y Wong
Frank W King
Shirley S Mihardja
Walter Liszewski
David J Erle
Randall J Lee
Harold S Bernstein
author_facet Carissa Ritner
Sharon S Y Wong
Frank W King
Shirley S Mihardja
Walter Liszewski
David J Erle
Randall J Lee
Harold S Bernstein
author_sort Carissa Ritner
collection DOAJ
description 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.
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spelling doaj.art-553dcc1c17fb4fd7909305ce9e91de3e2022-12-21T19:26:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1600410.1371/journal.pone.0016004An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.Carissa RitnerSharon S Y WongFrank W KingShirley S MihardjaWalter LiszewskiDavid J ErleRandall J LeeHarold S BernsteinUnlike 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.http://europepmc.org/articles/PMC3014940?pdf=render
spellingShingle Carissa Ritner
Sharon S Y Wong
Frank W King
Shirley S Mihardja
Walter Liszewski
David J Erle
Randall J Lee
Harold S Bernstein
An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
PLoS ONE
title An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
title_full An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
title_fullStr An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
title_full_unstemmed An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
title_short An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
title_sort engineered cardiac reporter cell line identifies human embryonic stem cell derived myocardial precursors
url http://europepmc.org/articles/PMC3014940?pdf=render
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