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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2020
Prepublished im Jahr
HGF-Berichtsjahr
2020
ISSN (print) / ISBN
2050-084X
e-ISSN
2050-084X
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 9,
Heft: ,
Seiten: ,
Artikelnummer: e55124
Supplement: ,
Reihe
Verlag
eLife Sciences Publications
Verlagsort
Sheraton House, Castle Park, Cambridge, Cb3 0ax, England
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s)
90000 - German Center for Diabetes Research
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502600-003
Förderungen
Copyright
Erfassungsdatum
2020-10-26