Id genes are essential for early heart formation

Thomas J. Cunningham; Michael S. Yu; Wesley L. McKeithan; Sean Spiering; Florent Carrette; Chun Teng Huang; Paul J. Bushway; Matthew Tierney; Sonia Albini; Mauro Giacca; Miguel Mano; Pier Lorenzo Puri; Alessandra Sacco; Pilar Ruiz-Lozano; Jean Francois Riou; Muriel Umbhauer; Gregg Duester; Mark Mercola; Alexandre R. Colas

doi:10.1101/gad.300400.117

Id genes are essential for early heart formation

Thomas J. Cunningham, Michael S. Yu, Wesley L. McKeithan, Sean Spiering, Florent Carrette, Chun Teng Huang, Paul J. Bushway, Matthew Tierney, Sonia Albini, Mauro Giacca, Miguel Mano, Pier Lorenzo Puri, Alessandra Sacco, Pilar Ruiz-Lozano, Jean Francois Riou, Muriel Umbhauer, Gregg Duester, Mark Mercola, Alexandre R. Colas^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

55 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1325-1338
Number of pages	14
Journal	Genes and Development
Volume	31
Issue number	13
DOIs	https://doi.org/10.1101/gad.300400.117
Publication status	Published - 1 Jul 2017

Keywords

Cardiac mesoderm specification
Cardiac progenitors
CRISPR/Cas9-mediated quadruple knockout
Heartless
Id proteins
Platform for cardiac disease modeling and drug discovery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cunningham, T. J., Yu, M. S., McKeithan, W. L., Spiering, S., Carrette, F., Huang, C. T., Bushway, P. J., Tierney, M., Albini, S., Giacca, M., Mano, M., Puri, P. L., Sacco, A., Ruiz-Lozano, P., Riou, J. F., Umbhauer, M., Duester, G., Mercola, M., & Colas, A. R. (2017). Id genes are essential for early heart formation. Genes and Development, 31(13), 1325-1338. https://doi.org/10.1101/gad.300400.117

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title = "Id genes are essential for early heart formation",

abstract = "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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Cunningham, TJ, Yu, MS, McKeithan, WL, Spiering, S, Carrette, F, Huang, CT, Bushway, PJ, Tierney, M, Albini, S, Giacca, M , Mano, M, Puri, PL, Sacco, A, Ruiz-Lozano, P, Riou, JF, Umbhauer, M, Duester, G, Mercola, M & Colas, AR 2017, 'Id genes are essential for early heart formation', Genes and Development, vol. 31, no. 13, pp. 1325-1338. https://doi.org/10.1101/gad.300400.117

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AU - Cunningham, Thomas J.

AU - Yu, Michael S.

AU - McKeithan, Wesley L.

AU - Spiering, Sean

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AU - Huang, Chun Teng

AU - Bushway, Paul J.

AU - Tierney, Matthew

AU - Albini, Sonia

AU - Giacca, Mauro

AU - Mano, Miguel

AU - Puri, Pier Lorenzo

AU - Sacco, Alessandra

AU - Ruiz-Lozano, Pilar

AU - Riou, Jean Francois

AU - Umbhauer, Muriel

AU - Duester, Gregg

AU - Mercola, Mark

AU - Colas, Alexandre R.

PY - 2017/7/1

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N2 - 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.

AB - 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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Id genes are essential for early heart formation

Abstract

Keywords

UN SDGs

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