PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Hong, L.* ; Li, N.* ; Gasque, V.* ; Mehta, S.* ; Ye, L.* ; Wu, Y.* ; Li, J.* ; Gewies, A. ; Ruland, J.* ; Hirschi, K.K.* ; Eichmann, A.* ; Hendry, C.* ; van Dijk, D.* ; Mani, A.*

Prdm6 controls heart development by regulating neural crest cell differentiation and migration.

JCI insight 7:e156046 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The molecular mechanisms that drive the acquisition of distinct neural crest cell (NCC) fates is still poorly understood. Here, we identify Prdm6 as an epigenetic modifier that temporally and spatially regulates the expression of NCC specifiers and determines the fate of a subset of migrating Cardiac NCCs (CNCCs). Using transcriptomic analysis, genetic and fate mapping approaches in transgenic mice, we show that disruption of Prdm6 is associated with impaired CNCC differentiation, delamination, and migration, and leads to patent ductus arteriosus (DA)and ventricular noncompaction. Bulk and single-cell RNA-seq analyses of DA and CNCC identify Prdm6 as a regulator of a network of CNCC specification genes including Wnt1, Tfap2b, and Sox9. Loss of Prdm6 in CNCCs diminishes its expression in pre-EMT cluster, resulting in the retention of NCC in the dorsal neural tube. This defect is associated with diminished H4K20 mono-methylation and G1-S progression and augmented Wnt1 transcript levels in pre-EMT and neural tube clusters, which we show is the major driver of the impaired CNCC migration. Altogether, these findings reveal Prdm6 as a key regulator of CNCC differentiation and migration and identify Prdm6 and its regulated network as potential targets for the treatment of congenital heart diseases.
Impact Factor
Scopus SNIP
Scopus
Cited By
Altmetric
9.484
1.308
4
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cardiology ; Cardiovascular Disease ; Development ; Embryonic Development ; Epigenetics; Smooth-muscle-cells; Ductus-arteriosus; Tfap2b Mutations; Expression; Apoptosis; Proliferation; Delamination; Methylation; Closure; System
Sprache englisch
Veröffentlichungsjahr 2022
HGF-Berichtsjahr 2022
ISSN (print) / ISBN 2379-3708
e-ISSN 2379-3708
Zeitschrift JCI insight
Quellenangaben Band: 7, Heft: 4, Seiten: , Artikelnummer: e156046 Supplement: ,
Verlag Clarivate
Verlagsort Ann Arbor, Michigan
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Signaling and Translation (SAT)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-509800-002
Förderungen NIH
DOI 10.1172/jci.insight.156046
WOS ID WOS:000760427500001
Scopus ID 85125020537
PubMed ID 35108221
Erfassungsdatum 2022-06-23
[➜Korrektur melden]