Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation

Sonia Stefanovic; Brigitte Laforest; Jean Pierre Desvignes; Fabienne Lescroart; Laurent Argiro; Corinne Maurel-Zaffran; David Salgado; Elise Plaindoux; Christopher De Bono; Kristijan Pazur; Magali Théveniau-Ruissy; Christophe Béroud; Michel Puceat; Anthony Gavalas; Robert G. Kelly; Stephane Zaffran

doi:10.7554/ELIFE.55124

Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation

Sonia Stefanovic, Brigitte Laforest, Jean Pierre Desvignes, Fabienne Lescroart, Laurent Argiro, Corinne Maurel-Zaffran, David Salgado, Elise Plaindoux, Christopher De Bono, Kristijan Pazur, Magali Théveniau-Ruissy, Christophe Béroud, Michel Puceat, Anthony Gavalas, Robert G. Kelly, Stephane Zaffran

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

33 Scopus citations

Abstract

Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.

Original language	English (US)
Article number	e55124
Pages (from-to)	1-32
Number of pages	32
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/ELIFE.55124
State	Published - Aug 2020
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.7554/ELIFE.55124

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Stefanovic, S., Laforest, B., Desvignes, J. P., Lescroart, F., Argiro, L., Maurel-Zaffran, C., Salgado, D., Plaindoux, E., De Bono, C., Pazur, K., Théveniau-Ruissy, M., Béroud, C., Puceat, M., Gavalas, A., Kelly, R. G., & Zaffran, S. (2020). Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation. eLife, 9, 1-32. Article e55124. https://doi.org/10.7554/ELIFE.55124

Stefanovic, S, Laforest, B, Desvignes, JP, Lescroart, F, Argiro, L, Maurel-Zaffran, C, Salgado, D, Plaindoux, E, De Bono, C, Pazur, K, Théveniau-Ruissy, M, Béroud, C, Puceat, M, Gavalas, A, Kelly, RG & Zaffran, S 2020, 'Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation', eLife, vol. 9, e55124, pp. 1-32. https://doi.org/10.7554/ELIFE.55124

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title = "Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation",

abstract = "Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.",

author = "Sonia Stefanovic and Brigitte Laforest and Desvignes, {Jean Pierre} and Fabienne Lescroart and Laurent Argiro and Corinne Maurel-Zaffran and David Salgado and Elise Plaindoux and {De Bono}, Christopher and Kristijan Pazur and Magali Th{\'e}veniau-Ruissy and Christophe B{\'e}roud and Michel Puceat and Anthony Gavalas and Kelly, {Robert G.} and Stephane Zaffran",

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year = "2020",

month = aug,

doi = "10.7554/ELIFE.55124",

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AU - Stefanovic, Sonia

AU - Laforest, Brigitte

AU - Desvignes, Jean Pierre

AU - Lescroart, Fabienne

AU - Argiro, Laurent

AU - Maurel-Zaffran, Corinne

AU - Salgado, David

AU - Plaindoux, Elise

AU - De Bono, Christopher

AU - Pazur, Kristijan

AU - Théveniau-Ruissy, Magali

AU - Béroud, Christophe

AU - Puceat, Michel

AU - Gavalas, Anthony

AU - Kelly, Robert G.

AU - Zaffran, Stephane

PY - 2020/8

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N2 - Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.

AB - Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxb1 in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxb1 in embryonic stem cells arrests cardiac differentiation, whereas Hoxb1-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxb1 and its paralog Hoxa1 results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.

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Hox-dependent coordination of mouse cardiac progenitor cell patterning and differentiation

Abstract

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