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Id genes are essential for early heart formation

Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional scree...

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Autores principales: Cunningham, Thomas J., Yu, Michael S., McKeithan, Wesley L., Spiering, Sean, Carrette, Florent, Huang, Chun-Teng, Bushway, Paul J., Tierney, Matthew, Albini, Sonia, Giacca, Mauro, Mano, Miguel, Puri, Pier Lorenzo, Sacco, Alessandra, Ruiz-Lozano, Pilar, Riou, Jean-Francois, Umbhauer, Muriel, Duester, Gregg, Mercola, Mark, Colas, Alexandre R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580654/
https://www.ncbi.nlm.nih.gov/pubmed/28794185
http://dx.doi.org/10.1101/gad.300400.117
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author Cunningham, Thomas J.
Yu, Michael S.
McKeithan, Wesley L.
Spiering, Sean
Carrette, Florent
Huang, Chun-Teng
Bushway, Paul J.
Tierney, Matthew
Albini, Sonia
Giacca, Mauro
Mano, Miguel
Puri, Pier Lorenzo
Sacco, Alessandra
Ruiz-Lozano, Pilar
Riou, Jean-Francois
Umbhauer, Muriel
Duester, Gregg
Mercola, Mark
Colas, Alexandre R.
author_facet Cunningham, Thomas J.
Yu, Michael S.
McKeithan, Wesley L.
Spiering, Sean
Carrette, Florent
Huang, Chun-Teng
Bushway, Paul J.
Tierney, Matthew
Albini, Sonia
Giacca, Mauro
Mano, Miguel
Puri, Pier Lorenzo
Sacco, Alessandra
Ruiz-Lozano, Pilar
Riou, Jean-Francois
Umbhauer, Muriel
Duester, Gregg
Mercola, Mark
Colas, Alexandre R.
author_sort Cunningham, Thomas J.
collection PubMed
description Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix–loop–helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation—Tcf3 and Foxa2—and activating inducers Evx1, Grrp1, and Mesp1. Most importantly, CRISPR/Cas9-mediated ablation of the entire Id (Id1–4) family in mouse embryos leads to failure of anterior cardiac progenitor specification and the development of heartless embryos. Thus, Id proteins play a central and evolutionarily conserved role during heart formation and provide a novel means to efficiently produce cardiovascular progenitors for regenerative medicine and drug discovery applications.
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spelling pubmed-55806542017-09-14 Id genes are essential for early heart formation Cunningham, Thomas J. Yu, Michael S. McKeithan, Wesley L. Spiering, Sean Carrette, Florent Huang, Chun-Teng Bushway, Paul J. Tierney, Matthew Albini, Sonia Giacca, Mauro Mano, Miguel Puri, Pier Lorenzo Sacco, Alessandra Ruiz-Lozano, Pilar Riou, Jean-Francois Umbhauer, Muriel Duester, Gregg Mercola, Mark Colas, Alexandre R. Genes Dev Research Paper Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix–loop–helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation—Tcf3 and Foxa2—and activating inducers Evx1, Grrp1, and Mesp1. Most importantly, CRISPR/Cas9-mediated ablation of the entire Id (Id1–4) family in mouse embryos leads to failure of anterior cardiac progenitor specification and the development of heartless embryos. Thus, Id proteins play a central and evolutionarily conserved role during heart formation and provide a novel means to efficiently produce cardiovascular progenitors for regenerative medicine and drug discovery applications. Cold Spring Harbor Laboratory Press 2017-07-01 /pmc/articles/PMC5580654/ /pubmed/28794185 http://dx.doi.org/10.1101/gad.300400.117 Text en © 2017 Cunningham et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Paper
Cunningham, Thomas J.
Yu, Michael S.
McKeithan, Wesley L.
Spiering, Sean
Carrette, Florent
Huang, Chun-Teng
Bushway, Paul J.
Tierney, Matthew
Albini, Sonia
Giacca, Mauro
Mano, Miguel
Puri, Pier Lorenzo
Sacco, Alessandra
Ruiz-Lozano, Pilar
Riou, Jean-Francois
Umbhauer, Muriel
Duester, Gregg
Mercola, Mark
Colas, Alexandre R.
Id genes are essential for early heart formation
title Id genes are essential for early heart formation
title_full Id genes are essential for early heart formation
title_fullStr Id genes are essential for early heart formation
title_full_unstemmed Id genes are essential for early heart formation
title_short Id genes are essential for early heart formation
title_sort id genes are essential for early heart formation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580654/
https://www.ncbi.nlm.nih.gov/pubmed/28794185
http://dx.doi.org/10.1101/gad.300400.117
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