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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.*

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

eLife 9:e55124 (2020)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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 subpopulations at genome-wide levels and demonstrate that Hoxbl negatively regulates differentiation in the posterior SHF. Spatial mis-expression of Hoxbl in the anterior SHF results in hypoplastic right ventricle. Activation of Hoxbl in embryonic stem cells arrests cardiac differentiation, whereas Hoxbl-deficient mouse embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking both Hoxbl and its paralog Hoxal results in atrioventricular septal defects. Our results show that Hoxbl 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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Publication type Article: Journal article
Document type Scientific Article
Keywords Cardiac Differentiation ; Congenital Heart Defect ; Developmental Biology ; Heart Development ; Hox ; Mouse ; Progenitor Cell ; Shf; 2nd Heart Field; Dorsal Mesenchymal Protrusion; Embryonic Stem-cells; Transcription Factors; Outflow Tract; Expression Analysis; Signaling Pathways; Arterial Pole; R Package; Seq
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Journal eLife
Quellenangaben Volume: 9, Issue: , Pages: , Article Number: e55124 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)