Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hedgehog-Responsive PDGFRa(+) Fibroblasts are Necessary for Maintenance of a Unique Pool of Alveolar Epithelial Progenitor Cells During Alveologenesis

ABSTRACT: The adult lung alveolus is a flexible 3D structure composed of multiple epithelial, endothelial, and mesenchymal cell types. Two highly specialized alveolar type I (AT1) and type II (AT2) cells, derived from epithelial progenitors, form the inner lining of the alveolus. During alveologenesis, the increasing demand for epithelial cells to cover the surface of the expansive number of alveoli is met by proliferating progenitor cells. There is presently little information about the identity of this population, and the niche microenvironment that controls its proliferation. We show that during alveologenesis genetic inactivation of TGFreceptors in hedgehog-responsive, PDGFRa(+) mesodermal cells previously identified as secondary crest myofibroblasts or SCMF reduces their number, and depletes a unique pool of proliferative epithelial progenitors, without significantly impacting differentiation of cells existing the pool. SCMF are a source of both extracellular matrix and secreted trophic molecules and may thus constitute a key component of the epithelial progenitor niche during alveologenesis. Paralleling the mouse model, we found evidence of reduced proliferation of SFTPC(+) progenitors in lungs of human preterm infants who died with bronchopulmonary dysplasia or BPD. SCMF are a transient cell population, which are depleted at completion of alveologenesis, making them a unique stage-dependent niche mesodermal cell type in mammalian organs.

ORGANISM(S): Mus musculus

PROVIDER: GSE172059 | GEO | 2021/04/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Emergence of Wnt signaling during lung alveologenesis expands and maintains the type 2 alveolar epithelial cell population

Project description:Alveologenesis is the culmination of lung development and involves the correct temporal and spatial signals to generate the delicate gas exchange interface. Using a novel Wnt signaling reporter system, we have identified a Wnt-responsive alveolar epithelial sublineage arising during alveologenesis called the axin2+ alveolar type 2 cell or AT2Aaxin2. The number of AT2Aaxin2 sublineage cells increases substantially during late lung development, revealing a wave of Wnt signaling during alveologenesis. Transcriptome analysis, in vivo clonal analysis, and ex vivo lung organoid assays reveal that AT2sAaxin2s promote enhanced AT2 cellalveolar growth during generation of the alveolus compared to the overall AT2 population. Activating Wnt signaling in the AT2 lineage results in expansion of the AT2axin2 sublineageAT2s whereas inhibition of Wnt signaling inhibits AT2 cell development and shunts alveolar epithelial development towards the AT1 cell lineage. These findings reveal a novel epithelial sublineage that coordinates Wnt-dependent alveolar growthAT2 expansion required for lung alveologenesis

2016-11-30 | GSE82154 | GEO

A mammalian Wnt5a–Ror2–Vangl2 axis controls the cytoskeleton and confers cellular properties required for alveologenesis

Project description:Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) within the saccules to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in both alveolar epithelial cells and myofibroblasts for alveologenesis. Our studies uncovered a Wnt5a–Ror2–Vangl2 cascade that endows cellular properties and thus novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior.

2020-03-03 | GSE140779 | GEO

Recombinant FGF10-induced de novo alveologenesis in neonatal mice after hyperoxia exposure is associated with enhanced AT2’s resident mesenchymal cell niche activity

Project description:Recombinant FGF10 improved hemodynamic measurements and alveologenesis. Alveolosphere assays indicate that the activity of rMC-Sca1Pos is negatively impacted by HYX and partially rescued by FGF10 treatment. scRNAseq results identified clusters expressing Fgf10, Fgf7, Pdgfra, Axin2 which could represent the rMC niche cells for the AT2 stem cells. In this syudy, we demonstrate that FGF10 administration is curative for BPD and identified a subpopulation of rMC-Sca1Pos niche cells which could represent its cellular target.

2022-06-29 | GSE190934 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [ATAC-seq]

Project description:The lung alveolus is the primary site of gas exchange in mammals. Within the alveolus, the alveolar type 2 (AT2) epithelial cell population generates surfactant to maintain alveolar structure and harbors a regenerative capacity to repair the alveolus after injury. We show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the AT2 cell population is critical for regenerating the alveolar niche. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a majority of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome, and functional phenotype with specific responsiveness to Wnt and FGF signaling that modulates differentiation and self-renewal, respectively. Importantly, human AEPs (hAEPs) can be isolated and characterized through a conserved surface marker and are required for human alveolar self-renewal and differentiation using alveolar organoid assays. Together, our findings show that AEPs are an evolutionarily conserved alveolar progenitor lineage essential for regenerating the alveolar niche in the mammalian lung.

2018-01-08 | GSE97052 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [mouse RNA-seq]

2018-01-08 | GSE97054 | GEO

Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor [human RNA-seq]

2018-01-08 | GSE97053 | GEO

Hedgehog-Responsive PDGFRa(+) Fibroblasts are Necessary for Maintenance of a Unique Pool of Alveolar Epithelial Progenitor Cells During Alveologenesis

Project description:Hedgehog-Responsive PDGFRa(+) Fibroblasts are Necessary for Maintenance of a Unique Pool of Alveolar Epithelial Progenitor Cells During Alveologenesis

| PRJNA721936 | ENA

The genomic, epigenomic and biophysical cues controlling the emergence of the gas exchange niche in the lung

Project description:The lung alveolus is the functional unit of the respiratory system required for gas exchange. During the transition to air breathing at birth, biophysical forces are thought to shape the emerging tissue niche. However, the intercellular signaling that drives these processes remain poorly understood. Applying a multimodal approach, we identify alveolar type 1 (AT1) epithelial cells as a distinct signaling hub. Lineage tracing demonstrates that AT1 progenitors align with receptive, force-exerting, myofibroblasts in a spatial and temporal manner. Through single cell chromatin accessibility and pathway expression (SCAPE) analysis, we demonstrate that AT1-restricted ligands are required for myofibroblasts and alveolar formation. These studies show that the alignment of cell fates, mediated by biophysical and AT1-derived paracrine signals, drives the extensive tissue remodeling required for postnatal respiration.

2021-03-11 | GSE149563 | GEO

Gpr116 regulates pulmonary surfactant pool size

2013-04-10 | GSE41417 | GEO

Gpr116 regulates pulmonary surfactant pool size

Project description:The amount of pulmonary surfactant within type II cells and in the alveolar space, referred to as surfactant pool sizes, are tightly regulated. The molecular pathways that sense and regulate surfactant pool size within the alveolus have not been identified and constitute a fundamental knowledge gap in the field. Our data show that mice with a germline mutation in the orphan G-protein-coupled receptor, GPR116, have a 30-fold accumulation of surfactant phospholipids that causes respiratory distress in adult animals. This phenotype is associated with increased surfactant secretion and induction of the purinergic receptor P2RY2 in young animals, and lipid-laden macrophages and alveolar destruction in older animals. We further demonstrate that GPR116 mRNA expression is developmentally regulated in the murine lung with peak expression at birth when surfactant pool sizes are maximal. Within the lung, GPR116 protein expression is restricted to the apical plasma membrane of alveolar type I and type II epithelial cells. To better understand the roles and molecular mechanisms by which Gpr116 influences gene expression in lung, the effect of cell-selective deletion of Gpr116 (Gpr116D/D) on genome-wide mRNA expression profiles was determined in murine type II alveolar epithelial cells. Differentially expressed genes were identified from Affymetrix Murine GeneChips analysis and subjected to gene ontology classification promoter analysis, pathway mapping and literature mining.

2013-04-10 | E-GEOD-41417 | 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