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https://hdl.handle.net/10316/108203
Título: | Id genes are essential for early heart formation | Autor: | 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. |
Palavras-chave: | cardiac progenitors; cardiac mesoderm specification; heartless; Id proteins; CRISPR/Cas9-mediated quadruple knockout; platform for cardiac disease modeling and drug discovery | Data: | 1-Jul-2017 | Editora: | Cold Spring Harbor Laboratory Press | Projeto: | This research was funded by grants from the National Institutes of Health (R01HL113601, R01HL128072, and R01HL130840 to M. Mercola; R44ES023521 to A.C.; P30 AR06130303 to M. Mercola, A.S., and P.L.P.; R01AR056712 and R01AR052779 to P.L.P.; and F31 AR065923-01 to M.T.), the Muscular Dystrophy Association (200845 to A.S.), the Fondation Leducq Transatlantic Alliance (Shapeheart), and the California Institute for Regenerative Medicine (CIRM; RC1-000132 to M. Mercola). S.A. was supported by the CIRM post-doctoral training program (TG2-01162). | Título da revista, periódico, livro ou evento: | Genes and Development | Volume: | 31 | Número: | 13 | Resumo: | 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. | URI: | https://hdl.handle.net/10316/108203 | ISSN: | 0890-9369 1549-5477 |
DOI: | 10.1101/gad.300400.117 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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Ficheiro | Descrição | Tamanho | Formato | |
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Id-genes-are-essential-for-early-heart-formationGenes-and-Development.pdf | 19.26 MB | Adobe PDF | Ver/Abrir |
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