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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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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. |
format | Online Article Text |
id | pubmed-5580654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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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