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Series GSE67889 Query DataSets for GSE67889
Status Public on Feb 12, 2016
Title Sequential Notch activation regulates ventricular chamber development
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Ventricular chambers are essential for the rhythmic contraction and relaxation that occurs in every hearbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is still poorly understood. Here we show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation and later coordinates ventricular patterning and compaction with coronary vessel development to give rise to the mature chamber via a temporal sequence of ligand signalling determined by the glycosyltransferase Manic Fringe (Mfng). The early endocardial expression of Mfng favours Dll4-Notch1 signalling, Which induces trabeculation in the developing ventricle.Ventricular maturation and compaction in turn require Mfng and Dll4 downregulation in the endocardium, Which allows myocardial Jag1- And Jag2- Signalling to Notch1 in this tissue.Timely and spatial perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies.
Overall design Dll4 and Notch1 conditional KOs using Nfact1 and/or Tie2 driven Cre expression: RNA was isolated from pooled whole hearts of 8 (Nfact1) or 9 (Tie2) E9.5 embryos per replicate. Dll4flox;Nfatc1-Cre and WT siblings (4 KO and 4 WT replicates), Notch1flox;Nfatc1-Cre and WT siblings (3 KO and 2 WT replicates), Dll4flox;Tie2-Cre and WT siblings (3 KO and 3 WT replicates). Jag1, Jag2 and Jag1Jag2 conditional KOs using cTnT driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. Jag1flox;cTnT-Cre and WT siblings (3 KO and 3 WT replicates), Jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). Jag1flox;jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). MFng Gain Of Function using Tie2 driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. MFng;Tie2-Cre and WT siblings (4 GOF and 4 WT replicates). For Dll4, Noth1 and Jag1 KOs, libraries were prepared using the standard Illumina TrueSeq RNASeq library preparation kit and sequenced in a GAIIx Illumina sequencer using a 75bp single end elongation protocol. For Jag2 and Jag1Jag2 KOs and MFng GOF libraries were prepared prepared using the NEBNext Ultra RNA Library Prep Kit for Illumina and sequenced in a HiSeq2500 Illumina sequencer using a 61bp single end elongation protocol
Contributor(s) D'Amato G, Luxán G, del Monte G, Martínez-Poveda B, Torroja C, Walter W, Bochter MS, Benedito R, Cole S, Martinez F, Hadjantonakis A, Uemura A, Jiménez-Borreguero LJ, de la Pompa JL
Citation(s) 26641715
Submission date Apr 14, 2015
Last update date Sep 08, 2022
Contact name Jose Luis de la Pompa
Organization name Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC).
Lab Intercellular Signalling in Cardiovascular Development & Disease
Street address Melchor Fernández Almagro 3
City Madrid
ZIP/Postal code 28029
Country Spain
Platforms (2)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (43)
GSM1657594 Dll4KO-Nfat_1
GSM1657595 Dll4KO-Nfat_2
GSM1657596 Dll4KO-Nfat_3
BioProject PRJNA281121
SRA SRP057171

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE67889_D4NFKOvsWT.D4T2KOvsWT.NormCounts.csv.gz 1.2 Mb (ftp)(http) CSV
GSE67889_J1andJ2andJ12.NormCounts.txt.gz 1.4 Mb (ftp)(http) TXT
GSE67889_MFng.NormCounts.txt.gz 920.1 Kb (ftp)(http) TXT
GSE67889_NINFKOvsWT.NormCounts.csv.gz 772.5 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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