Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microstructures regulate distant cellular interactions during heart formation

ABSTRACT: Communication between endocardium and myocardium, separated by cardiac jelly, is essential for cardiac morphogenesis. How membrane-localized receptors and ligands achieve interaction across the cardiac jelly is not understood. Utilizing a number of approaches, including genetic labeling of cell-cell contacts, we found that myocardium and endocardium interact directly via microstructures, termed Tunneling Nanotube-Like microstructures (TNTLs). TNTLs extend from cardiomyocytes to directly contact endocardial cells (ECs). TNTLs transport cytoplasmic proteins, transduce signals between cardiomyocytes and ECs, and initiate myocardial growth toward the lumen to form ventricular trabeculae-like structures. Loss of TNTLs disturbs signaling interactions and, subsequently, ventricular patterning.

ORGANISM(S): Mus musculus

PROVIDER: GSE279629 | GEO | 2024/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Myocardial Bmp2 overexpression leads to ectopic cardiac EMT and promotes chamber cardiomyocyte proliferation and immaturity

Project description:Defective valve and septa formation constitute a substantial part of congenital heart defects affecting the neonate or the adult. During cardiac development, restricted myocardial Bmp2 expression is a key signal for the specification and patterning of the valve-forming field in the atrio-ventricular canal (AVC) region and the initiation of the epithelial-mesenchyme transition (EMT) that gives rise to the valve primordia. We have generated a mouse transgenic line conditionally expressing Bmp2. Nkx2.5Cre-driven Bmp2 overexpression in the myocardium leads to foetal lethality, due to valve and chamber dysmorphogenesis, and rescue of the AVC specification defect of Bmp2-null embryos. Nkx2.5Cre/+;Bmp2tg/+ transgenic embryos show ventricular septal defect, thickened valves, enlarged trabeculae and dilated ventricles, whose endocardium is able to undergo EMT when explanted onto collagen gels. Gene profile and marker analysis indicates that cellular proliferation is increased and chamber differentiation and patterning is impaired in Nkx2.5Cre/+;Bmp2tg/+ embryos, but the ventricular-specific gene expression program is not abolished. We obtained similar results using a second myocardial driver (cTnTCre) to activate Bmp2 expression, but not with an endothelial-specific one (Tie2Cre), as Tie2Cre/+;Bmp2tg/+ mice are normal and survive to adulthood, indicating that Bmp2 must emanate from the myocardium to exert its EMT-driving and cardiomyocyte maturation blocking effect. Forced Bmp2 expression in vitro stimulates EBs proliferation and blocks their progression into cardiomyogenesis, an effect partially rescued by Noggin. These data show that widespread myocardial Bmp2 expression directs ectopic valve primordium formation and maintains chamber myocardium and early cardiac progenitors in a primitive, proliferative state, identifying Bmp2 as a potential factor for the expansion of immature cardiomyocytes.

2018-04-11 | GSE100810 | GEO

Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy

Project description:Left ventricular noncompaction (LVNC) Causes prominent ventricular trabeculations and reduces cardiac systolic function. The clinical presentation of LVNC ranges from asymptomatic to heart failure. We show that germline mutations in human MIB1 (mindbomb homolog 1), which encodes an E3 ubiquitin ligase that promotes endocytosis of the NOTCH ligands DELTA and JAGGED, cause LVNC in autosomal-dominant pedigrees, with affected individuals showing reduced NOTCH1 activity and reduced expression of target genes. Functional studies in cells and zebrafish embryos and in silico modeling indicate that MIB1 functions as a dimer, which is disrupted by the human mutations. Targeted inactivation of Mib1 in mouse myocardium causes LVNC, a phenotype mimicked by inactivation of myocardial Jagged1 or endocardial Notch1. Myocardial Mib1 mutants show reduced ventricular Notch1 activity, expansion of compact myocardium to proliferative, immature trabeculae and abnormal expression of cardiac development and disease genes. These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction. RNA was isolated from the ventricles of 16 WT and 16 Mib1flox; CTnT-cre hearts at E14.5 and then pooled into four replicates.

2015-08-10 | E-GEOD-71912 | biostudies-arrayexpress

Tie2 regulates endocardial sprouting and myocardial trabeculation

Project description:The ang1-Tie2 pathway is required for normal vascular development, but its molecular effectors are not well-defined during cardiac ontogeny. Here we show that endocardial specific attenuation of Tie2 results in mid-gestation lethality due to heart defects associated with a hyperplastic but simplified trabecular meshwork (fewer but thicker trabeculae). Reduced proliferation and production of endocardial cells (ECs) following endocardial loss of Tie2 results in decreased endocardial sprouting required for trabecular assembly and extension. The hyperplastic trabeculae result from enhanced proliferation of trabecular cardiomyocyte (CMs), which is associated with upregulation of Bmp10, increased retinoic acid (RA) signaling, and Erk1/2 hyperphosphorylation in the myocardium. Intriguingly, myocardial phenotypes in Tie2-cko hearts could be partially rescued by inhibiting in utero RA signaling with pan-retinoic acid receptor antagonist BMS493. These findings reveal two complimentary functions of endocardial Tie2 during ventricular chamber formation: ensuring normal trabeculation by supporting EC proliferation and sprouting, and preventing hypertrabeculation via suppression of RA signaling in trabecular CMs.

2019-05-07 | GSE130741 | GEO

Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy

2015-08-10 | GSE71912 | GEO

Embryonic VHL-HIF signaling defines dynamic heart metabolic compartments essential for cardiac maturation

Project description:While gene regulatory networks involved in cardiogenesis have been characterized, the role of bioenergetics remains less studied. Here we show that until midgestation, myocardial metabolism is compartmentalized, with a glycolytic signature restricted to compact myocardium contrasting with increased mitochondrial oxidative activity in the trabeculae. HIF1a regulation mirrors this pattern, with expression predominating in compact myocardium and scarce in trabeculae. By midgestation, the compact myocardium downregulates HIF1a and switches toward oxidative metabolism. Deletion of the E3 ubiquitin ligase Vhl results in HIF1a hyperactivation, disrupting metabolic compartmentalization and blocking the midgestational shift toward oxidative phosphorylation. Moreover, the altered glycolytic signature induced by HIF1 trabecular activation precludes regulation of genes essential for cardiac conduction system establishment. Our findings reveal VHL-HIF-mediated metabolic compartmentalization in the developing heart and the connection between metabolism and myocardial differentiation. These results highlight the importance of bioenergetics in ventricular myocardium specialization and its potential relevance to congenital heart disease.

2016-12-19 | GSE89733 | GEO

The ion channel Trpc6a regulates the cardiomyocyte regenerative response to mechanical stretch

Project description:Myocardial damage caused for example by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In adult mammals, these changes trigger an adaptive cardiomyocyte hypertrophic response which, if the damage is extensive, will ultimately lead to pathological hypertrophy and heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in the adult zebrafish heart and neonatal mice proliferate and completely regenerate the damaged myocardium. We therefore hypothesized that in adult zebrafish, changes in mechanical loading due to myocardial damage may act as a trigger to induce cardiac regeneration. Based, on this notion we sought to identify mechanosensors which could be involved in detecting changes in mechanical loading and triggering regeneration. Here we show using a combination of knockout animals, RNAseq and in vitro assays that the mechanosensitive ion channel Trpc6a is required by cardiomyocytes for successful cardiac regeneration in adult zebrafish. Furthermore, using a cyclic cell stretch assay, we have determined that Trpc6a induces the expression of components of the AP1 transcription complex in response to mechanical stretch. Our data highlights how changes in mechanical forces due to myocardial damage can be detected by mechanosensors which in turn can trigger cardiac regeneration.

2023-12-20 | E-MTAB-13603 | biostudies-arrayexpress

Transcription profiling by array and functional characterization of developing cardiomyocytes from recombinant murine embryonic stem cells

Project description:Here, we characterize the transcriptome of the mouse embryonic stem cell line CM7-1 during differentiation into beating cardiomyocytes and compared the gene expression profiles with those from primary adult murine cardiomyocytes and left ventricular myocardium.

2009-03-21 | E-MEXP-1405 | biostudies-arrayexpress

Transcriptome-guided functional analyses reveal novel biological properties and regulatory heirarchy of human embryonic stem cell derived ventricular cardiomyocytes.

Project description:Profiling global gene expression of undifferentiated human embryonic stem cells, artificially derived cardiomyocytes, fetal ventricular cardiomyocytes, and adult ventricular cardiomyocytes to determine transcriptomic variation between these cell types. Total RNA extracted from 10 human samples representing four stages of cardiac development from undifferentiated stem cells to mature adult cardiac tissue.

2013-09-10 | E-GEOD-50704 | biostudies-arrayexpress

Transcriptome and translatome of cardiomyocytes exposed to hypoxia in vivo and in vitro

Project description:Adult Cardiac hypoxia as a crucial pathogenesis factor can induce detrimental effects on cardiac injury and dysfunction. The global transcriptome and translatome reflecting the cellular response to hypoxia have not yet been extensively studied in myocardium. In this study, adult rats were subjected to acute normobaric hypoxia at 10% oxygen with 10 min (mild hypoxia) and 30 min (severe hypoxia). Rat H9C2 cardiomyocytes were treated with the culture condition (1% O2, 94% N2, and 5% CO2) for mild hypoxia (8 hr) and severe hypoxia(24 hr). We then conducted RNA-seq and Ribo-seq in non-infarcted left ventricular myocardial tissues and H9C2 cells exposed to different periods of hypoxia stress in vivo and in vitro.

2020-10-23 | E-MTAB-9541 | biostudies-arrayexpress

Gene expression in mouse embyonic cardiomyocytes, fibroblasts and adult cardiac fibroblasts

Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. To identify candidate fibroblast-derived factors that promote myocyte proliferation, we isolated RNA from Nkx-YFP+ cardiomyocytes, embryonic cardiac fibroblasts, and adult cardiac fibroblasts and profiled mRNA expressions by microarray analyses. Arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of mouse embyonic cardiomyocytes, fibroblasts and adult cardiac fibroblasts.

2009-01-14 | E-GEOD-14412 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data