Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Using Next Generation Sequencing to identify molecular pathways that are regulated by cardiac lymphatics during heart development

ABSTRACT: Our study has identified a novel regulatory role of cardiac lymphatics in heart development, particularly in cardiomyocyte proliferation and survival. To investigate the molecular basis of this cardiac lymphatics-dependent effects, We then performed RNA sequencing (RNA-seq) of the ventricular portions of E17.5 controls and Prox1 conditional nulls (embryos devoid of cardiac lymphatic development). Gene set expression analysis (GSEA) revealed that in Prox1 conditional null hearts, genes and pathways related to cell cycle were greatly reduced; instead, expression of genes and pathways involved in apoptosis were enriched. Our study has identified a novel regulatory role of cardiac lymphatics in heart development, particularly in cardiomyocyte proliferation and survival. To investigate the molecular basis of this cardiac lymphatics-dependent effects, We then performed RNA sequencing (RNA-seq) of the ventricular portions of E17.5 controls and Prox1 conditional nulls (embryos devoid of cardiac lymphatic development). Gene set expression analysis (GSEA) revealed that in Prox1 conditional null hearts, genes and pathways related to cell cycle were greatly reduced; instead, expression of genes and pathways involved in apoptosis were enriched.

ORGANISM(S): Mus musculus

PROVIDER: GSE158504 | GEO | 2020/09/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Atlas of lymphangiogenesis [scRNA-Seq]

Project description:During development, lymphatic vasculature forms as a second and distinct network that derives from embryonic blood vessels. Transdifferentiation of venous endothelial cells into specified lymphatic endothelial cells (LECs) is the first step in this process. Transdifferentiation and specification of LEC fate requires Prox1, but how Prox1 regulates transdifferentiation and differentiation is not fully understood. We present a single cell transcriptomic atlas of lymphangiogenesis spanning four key developmental stages that reveals new markers and functional regulators of lymphatic development. We extend this to comprehensively profile single cell transcriptomic and chromatin changes controlled by Prox1 using zygotic prox1a mutants, which form lymphatics that then dedifferentiate. Combining this with single cell analysis of Prox1-null, double prox1a/prox1b maternal zygotic mutants, we reveal in depth the role of Prox1 in control of LEC fate specification and differentiation. This resource reveals dual and progressive functions for Prox1, blocking blood vascular and hematopoietic fate while simultaneously up-regulating a small number of early acting genes that include tspan18a/b and lgals3a/b which are essential for lymphangiogenesis. This embryonic developmental resource will serve as a baseline to better understand both developmental and pathological lymphangiogenesis in the future. [Citations in sample metadata correspond to reference numbers in the associated publication.]

2023-04-27 | GSE188341 | GEO

Atlas of lymphangiogenesis [scATAC-Seq]

2023-04-27 | GSE188340 | GEO

Bulk RNA-seq of sham or alkali injury treated WT and Vegfr3 depletion mouse iris

Project description:We report conditional ablation of lymphatic Vegfr3 alleviated inflammatory process in alkali injured iris. Prox1CreERT2 mice were crossed with Vegfr3fl/fl to selectively target gene expression in Prox1+ lymphatic cells. Injury models were established at 6 weeks postnatally, and Vegfr3 gene depletion was conducted via Tamoxifen injection on the day 13th-17th after corneal alkali injury. Mice were sacrificed 28th days post-injury.

2024-05-29 | GSE240269 | GEO

Transcriptomic profiling of vegfc(hy-/-);vegfd(-/-) mutant hearts reveals that vegfc/d signaling and lymphatics vasculature play a role in cardiac metabolism [fresh tissue]

Project description:Recent studies have suggested that promoting lymphangiogenesis enhances cardiac repair following injury, but it is unknown whether lymphangiogenesis is required for cardiac regeneration. Here, we describe the anatomical distribution, regulation and function of the cardiac lymphatic network in a highly regenerative zebrafish model system using transgenic reporter lines and loss-of-function approaches.To understand the transcriptional profile of the model, we performed RNA-seq on cardiac ventricles from control and mutant (vegfc(hy-/-);vegfd(-/-)) ventricles. Overall, vegfc(hy-/-;vegfd-/-) mutant ventricles were characterized by an up-regulation of pathways related to sphingolipid and phospholipid metabolism, translation, protein maturation and nonsense mediated decay compared to control hearts. Our findings suggest that lymphatics vasculature play a role in lipid transport and when lymphatic function is compromised in vegfch(y-/-;vegfd-/-) mutant, there are consequences to sphingolipid and phospholipid metabolism. Vegfc(hy-/-;vegfd-/-) mutant ventricles were not characterized by an enrichment of genes pathways implicated in pathological hypertrophy. This finding suggests that the absence of cardiac lymphatics induced a physiological rather than pathological cardiac hypertrophy.

2019-09-03 | GSE133130 | GEO

Label free DIA proteomic analysis of thoracic lymph from cigarette smoke (CS)-exposed mice

Project description:The lymphatic vasculature is critical for lung function, but defects in lymphatic functionin the pathogenesis of lung disease is understudied. To further assess the contribution of lymphatics to the pathogenesis of lung emphysema we used a mouse model of cigarette smoke (CS)-induced emphysema, and analyzed lung lymphatics using immunohistochemistry, functional assays, and confocal microscopy. Additionally, we further harvested thoracic lymph from CS-exposed mice for proteomic analysis. In this presented section of our research, we highlight the label free quantitative DIA proteomics approaches used to profile the proteomic and peptidomics changes in the lymph from cigarette smoke (CS)-mice as compared with the lymph proteome from mice exposed to room air. Label free quantitative DIA proteomics analysis of lymph confirmed upregulation of coagulation and inflammatory pathways in the lymphatics of CS-exposed mice compared to control mice.

2022-05-10 | PXD031413 | Pride

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [RNA-seq]

Project description:Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development. Here, we describe a novel enhancer element important for regulating Prox1 expression in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. CRISPR-Cas9 genome editing of this enhancer element revealed that deletion of only 5 nucleotides encompassing the GATA2 binding site has a dramatic impact on lymphatic vascular development; mice homozygous for this deletion die soon after birth exhibiting profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice exhibit reduced levels of genes characteristic of lymphatic endothelial cell identity and acquire characteristics of hemogenic endothelium, including the capacity to generate hematopoietic cells. These data reveal the first transcriptional enhancer element important for regulating Prox1 expression and lymphatic endothelial cell identity and suggest that Prox1 is important for repressing hemogenic cell identity in the lymphatic endothelium.

2022-11-21 | GSE129633 | GEO

Lymphatic endothelial cell identity is controlled by a GATA2 bound enhancer [ChIP-seq]

2022-11-21 | GSE129632 | GEO

RNAi profiling of human lymphatic endothelial cells after knockdown of Prox1 and/or NR2F2

Project description:Gene expression profiles of primary lymphatic endothelial cells (LECs) isolated from human foreskin were analyzed after siRNA-mediated knockdown of control (firefly luciferase), Prox1, NR2F2 or Prox1/NR2F2 for 48 hours. Experiment Overall Design: Passage five human lymphatic endothelial cells (LECs) were cultured on fibronectin (10 Î¼g/ml)-coated plates in a complete media (EBM, 20% FBS supplemented with 10 Î¼g/ml hydrocortisone acetate, 25 ug/ml cAMP and antibiotics). LECs were harvested and electorporated with siRNA duplexes for 48 hours with siRNA duplexes against either firefly luciferase(control), Prox1, NR2F2 or Prox1/NR2F2. Total RNA was purified using Tri-reagent and was subjected to microarray analysis. Experiment Overall Design:

2008-10-25 | E-GEOD-12846 | biostudies-arrayexpress

Gene expression analysis of mouse lymphatic endothelial cells (LECs) from the subcapsular sinus (SS, afferent) and lymphatic sinus (LS, efferent)

2016-08-24 | GSE68371 | GEO

Gene expression analysis of mouse lymphatic endothelial cells (LECs) from the subcapsular sinus (SS, afferent) and lymphatic sinus (LS, efferent)

Project description:Afferent lymphatic vessels bring antigens and diverse populations of leukocytes to draining lymph nodes, but efferent lymphatics allow only lymphocytes to leave the nodes. Despite fundamental importance of afferent vs. efferent lymphatics in immune response and cancer spread, molecular characteristics of these different arms of the lymphatic vasculature are largely unknown. In this work we report marked transcriptional differences between afferent and efferent lymphatic endothelial cells. Mouse inguinal, axillary, and brachial lymphnodes were collected and cryomolds prepared for laser-capture microdissection. Frozen sections were stained with various cell marker antibodies and micro-dissection performed to collect lymphatic endothelial cells. Total RNA was extracted from the cells and used in microarray analysis. Alternatively, popliteal, caudal, lumbar, inguinal, mesenteric, renal, axillary, brachial, deep and superficial cervical LN were enzymatically digested, the cells stained, and FACs sorted before RNA isolation.

2016-08-24 | E-GEOD-68371 | 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