Single cell evaluation of endocardial Hand2 gene regulatory networks reveals HAND2-dependent pathways that impact cardiac morphogenesis.
Cardiogenesis
Congenital heart defects
Endocardial development
HAND factors
Mouse
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
15 02 2023
15 02 2023
Historique:
received:
30
09
2022
accepted:
26
12
2022
pmc-release:
06
02
2024
pubmed:
10
1
2023
medline:
9
2
2023
entrez:
9
1
2023
Statut:
ppublish
Résumé
The transcription factor HAND2 plays essential roles during cardiogenesis. Hand2 endocardial deletion (H2CKO) results in tricuspid atresia or double inlet left ventricle with accompanying intraventricular septum defects, hypo-trabeculated ventricles and an increased density of coronary lumens. To understand the regulatory mechanisms of these phenotypes, single cell transcriptome analysis of mouse E11.5 H2CKO hearts was performed revealing a number of disrupted endocardial regulatory pathways. Using HAND2 DNA occupancy data, we identify several HAND2-dependent enhancers, including two endothelial enhancers for the shear-stress master regulator KLF2. A 1.8 kb enhancer located 50 kb upstream of the Klf2 TSS imparts specific endothelial/endocardial expression within the vasculature and endocardium. This enhancer is HAND2-dependent for ventricular endocardium expression but HAND2-independent for Klf2 vascular and valve expression. Deletion of this Klf2 enhancer results in reduced Klf2 expression within ventricular endocardium. These data reveal that HAND2 functions within endocardial gene regulatory networks including shear-stress response.
Identifiants
pubmed: 36620995
pii: 286290
doi: 10.1242/dev.201341
pmc: PMC10110492
pii:
doi:
Substances chimiques
Transcription Factors
0
Hand2 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : P01 HL134599
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE029091
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145060
Pays : United States
Organisme : NIH HHS
ID : 1R01DE02909
Pays : United States
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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