Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mapping pulmonary endothelial cell heterogeneity at homeostasis and during tissue regeneration

ABSTRACT: Pulmonary endothelial cells are an essential component of the lung alveolus, where they assist in integrating this niche with the cardiovascular system to perform gas exchange with the external environment. Despite its importance, the extent and function of endothelial cell heterogeneity within the lung remains incompletely understood. Using single-cell analytics, we show that multiple vascular endothelial cell populations exist in the mouse lung, including macrovascular endothelium (maECs), microvascular endothelium (miECs), and a new population we have termed regulator endothelium (RECs). RECs express a unique gene signature including elevated expression of Cd34 (Cd34high), Vegfr2 (Kdr), Ednrb, and Car4. The location of RECs within the lung is similar to other miECs at homeostasis, but they appear to preferentially invest regions of regenerating lung tissue after acute lung injury. Receptor-ligand analysis indicates that RECs are primed to receive reparative signals from alveolar type I cells through Vegfa-Vegfr2. Interestingly, influenza infection reveals the emergence of a highly proliferative endothelial cell population (PECs) that likely contributes to revascularization of the alveolar space after injury and may arise from Cd34low miECs. These studies map endothelial cell heterogeneity in the adult lung and characterize the preferential response of novel endothelial cell subpopulations required for proper tissue regeneration after acute lung injury.

ORGANISM(S): Mus musculus

PROVIDER: GSE128944 | GEO | 2020/02/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung [bulk RNA-seq]

Project description:The lung microvasculature is essential for gas exchange and commonly considered homogeneous. We show that Vascular endothelial growth factor A (Vegfa) from the epithelium specifies a distinct endothelial cell (EC) population in the postnatal mouse lung. Vegfa is predominantly expressed by alveolar type 1 (AT1) cells and locally required to specify a subset of ECs. Single cell RNA-seq identified 15~20% lung ECs as transcriptionally distinct and marked by Carbonic anhydrase 4 (Car4), which are specifically lost upon epithelial Vegfa deletion. Car4 ECs, unlike bulk ECs, have extensive cellular projections and are separated from AT1 cells by a limited basement membrane without any intervening pericytes. Without Car4 ECs, the alveolar space is aberrantly enlarged despite the normal appearance of myofibroblasts. Lung Car4 ECs and retina tip ECs have common and distinct transcriptional profiles. These findings support a signaling role of AT1 cells and shed light on alveologenesis.

2020-01-01 | GSE124324 | GEO

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung [scRNA-seq]

2020-01-01 | GSE124323 | GEO

FGF-dependent regulation of VEGF signaling via transcriptional control of VEGF receptor 2 expression

Project description:Numerous studies have suggested a link between fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) signaling pathways; however the nature of this link has not been established. To evaluate this relationship we investigated VEGF signaling in endothelial cells with disrupted FGF signaling in vitro and in vivo. We find that endothelial cells lacking FGF signaling become unresponsive to VEGF due to down regulation of VEGFR2 expression caused by reduced Vegfr2 enhancer activation, which is in turn caused by reduced activation of Ets family transcription factors. In vivo this manifests in the loss of vascular integrity and morphogenesis. Thus, basal FGF stimulation of the endothelium is required for maintenance of VEGFR2 expression and the ability to respond to VEGF stimulation and accounts for the hierarchic control of vascular formation by FGFs and VEGF. Primary mouse lung endothelial cells were transduced with either Adeno-Null (empty) or Adeno- dominant negative FGF receptor 1 and harvested 24 hours after transduction. Total RNA was extracted and subjected to the analysis using SuperArray GEArray Q Series Mouse Angiogenesis Gene Array. Comparisons were made between treatments.

2011-06-07 | E-GEOD-28483 | biostudies-arrayexpress

Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through Notch signaling

Project description:Radiation-induced lung injury is a common late side-effect of thoracic radiotherapy. The inflammatory microenvironment plays a key role in this process. Endothelial cells are the goalkeeper of inflammation. Endothelial dysfunction following leukocytes infiltrated is a prominent feature in the pathogenesis of radiation-induced lung injury. Tyrosine phosphatase Shp2 is a key regulator of endothelial functions and inflammation. Here, we established a clinical-mimicking mouse model of radiation-induced lung injury and found that Shp2 activity was elevated in endothelium after injury. Mice with endothelium-specific Shp2 deletion showed relieved collagen deposition along with disrupted radiation-induced Jag1 expression in the endothelium. Furthermore, endothelium-derived Jag1 activated the alternative activation of macrophages in vitro and in vivo by paracrine Notch signaling. Consistently, Notch pathway was significant activated by chest irradiation in the peripheral blood leukocytes of cancer patients. Collectively, this is the first demonstration of radiation-induced lung injury regulation by endothelial Shp2. Shp2 participates in the radiation-induced endothelial dysfunction and subsequently inflammatory microenvironment producing.

2021-12-18 | GSE191056 | GEO

ATF3 promotes endothelial cell response to acute lung injury

Project description:Following acute injury, the capillary vascular bed in the lung must be repaired to reestablish gas exchange between pulmonary endothelial cells (ECs) lining these vessels and the alveolar epithelium. However, the factors that control EC stress response and drive regeneration of pulmonary capillaries remain incompletely understood. Viral infections such as influenza and COVID-19 may indirectly damage lung vasculature through loss of epithelial gas exchange partners or through signaling from infiltrating immune cells. To prevent excessive tissue damage and to renew the endothelium, ECs must both withstand cellular stress and proliferate after injury. Here, we show that the transcription factor and immediate early gene Atf3 is essential for both responses in the mouse lung after influenza infection. Atf3 expression defines a subpopulation of capillary ECs enriched in genes involved in cellular response to stress, angiogenesis, and vascular development. Endothelial loss of ATF3 results in defective alveolar regeneration: in the absence of ATF3, ECs exhibit increased apoptosis and decreased proliferation, resulting in an emphysema-like phenotype with enlarged alveolar airspaces lined with regions of lost vasculature. These data implicate ATF3 as an essential component of the vascular response to acute lung injury that is required for successful lung regeneration.

2023-05-19 | GSE213475 | GEO

Transcription profiling of human platelets as cytotoxic mediators in sepsis-induced acute lung injury (ALI)

Project description:ALI is one of the most common disease processes in adult and pediatric intensive care units and results in significant morbidity and mortality. The pathophysiology of ALI begins with a massive pro-inflammatory response likely mediated by as yet uncharacterized platelet/endothelium interactions with macrophage activation. This leads to a cytokine/chemokine cascade producing endothelial disruption. Neutrophilic infiltration of the alveolar wall and alveolar space with a concomitant procoagulant state develops. Despite the fact that inadequate understanding of ALI pathophysiology remains a barrier to effective treatment, novel therapeutics including ventilatory manipulations and anti-inflammatory molecules are beginning to improve the morbidity and mortality associated with this disease process. Experiment Overall Design: Acute Lung Injury (ALI) represents a spectrum of critical pulmonary illness in which inflammatory processes lead to varying degrees of alveolar damage and respiratory failure. ALI is a common disease process in the intensive care unit (ICU) with high morbidity and mortality. Based on new insights into the molecular processes of lung injury, we hypothesize that a temporal analysis of cells of innate immunity and thrombosis will demonstrate changes in mRNA and protein expression that are significantly associated with progression of ALI. Additionally, the analysis of the resulting datasets will lead to an unprecedented understanding of the pathogenesis of ALI.

2008-06-11 | E-GEOD-10361 | biostudies-arrayexpress

A human alveolus-on-chip model for studying radiation induced lung injury

Project description:Acute exposure to high-dose gamma radiation often results in radiation-induced lung injury (RILI), characterized by acute pneumonitis and subsequent lung fibrosis. A microfluidic organ-on-a-chip device consisting of human lung alveolar epithelium and pulmonary endothelium (Lung Alveolus Chip) is used to recapitulate acute, early stage RILI in vitro. This RNA-seq data captures that both the lung epithelium and endothelium in this model capture key hallmarks of this disease particularly, DNA damage, cellular hypertrophy, upregulation of inflammatory cytokines, and loss of barrier function within 6h of radiation exposure. The data also suggests that radiation affects the alveolar endothelium more significantly than the epithelium. The alveolus chips are exposed to radiation injury at 16 Gy and shows effects that resemble the human lung greater than animal preclinical models. These data demonstrate that the Lung Alveolus Chip provides a human relevant alternative approach for studying the molecular basis of acute RILI towards screening radiation countermeasure therapeutics.

2023-09-11 | GSE242840 | GEO

Lung selective gene responses to alveolar hypoxia

Project description:Pulmonary hypoxia is a common complication of chronic lung diseases leading to the development of pulmonary hypertension. The underlying sustained increase in vascular resistance in hypoxia is a response unique to the lung. Thus, we hypothesised that there are genes whose expression is altered selectively in the lung in response to alveolar hypoxia. Using a novel subtractive array strategy, we compared gene responses to hypoxia in primary human pulmonary microvascular endothelial cells to those in cardiac microvascular endothelium and identified genes selectively differentially regulated in the lung endothelium. Keywords: Time course, cell type comparison

2008-11-21 | GSE11341 | GEO

Global gene expression profiling of endothelial cells from different vascular bed and caliber

Project description:Endothelial cells (EC) were obtained from commercial source (Lonza), expanded and culture until passage 3. HMVEC-LBI correspond to lung microvascular endothelial cells, HPAEC to lung macrovascular endothelial cells, HAEC to cardiac macrovascular endothelial cells and HMVEC-C to cardia microvascular endothelial cells. These cells presented different capacity to generate endothelial microvesicles. The objective of the study was to identify differentially genes between these cells to understand this difference. Total RNA was extracted using the mirVana miRNA Isolation Kit (Ambion), according to the manufacturer’s recommendations. Cy3-CTP labeled RNA was prepared according to standard Agilent protocol from 400ng total RNA. The hybridization was performed for 17 hrs at 65°C. cRNA labeling and hybridization performance were performed and all parameters checked were found within the manufacturers specifications. Arrays were scanned as described in the manufacturers’ protocol. Signal intensities on 20 bit tiff images were calculated by Feature Extraction software (FE, Version 8.5; Agilent Technologies). Data analyses were conducted with GeneSpring GX software (Vers.12.6; Agilent Technologies)

2023-01-30 | E-MTAB-4886 | biostudies-arrayexpress

mouse lung endothelial single cell transcriptomics

Project description:Disruption of pulmonary vascular homeostasis is a central feature of viral pneumonia, wherein endothelial cell (EC) death and subsequent angiogenic responses represent critical determinants of the outcome of severe lung injury. A more granular understanding of the fundamental mechanisms driving reconstitution of the lung endothelium is necessary to facilitate therapeutic targeting of vascular repair. Here, we applied single-cell RNA sequencing (scRNA-seq) to profile lung ECs from mice on D0, D20 and D30 post influenza infection. Our data revealed the dynamics of endothelial subsets during influenza injury.

2023-12-10 | GSE201631 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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