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Epithelial Vegfa specifies a distinct endothelial population in the mouse lung

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE124325 | GEO | 2020/01/01

REPOSITORIES: GEO

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Epithelial Vegfa Specifies a Distinct Endothelial Population in the Mouse Lung.

Project description:The lung microvasculature is essential for gas exchange and commonly considered homogeneous. We show that VEGFA from the epithelium is required for a distinct endothelial cell (EC) population in the mouse lung. Vegfa is predominantly expressed by alveolar type 1 (AT1) cells and locally required to specify a subset of ECs. Single-cell RNA sequencing (scRNA-seq) reveals that ∼15% of lung ECs are transcriptionally distinct-marked by Carbonic anhydrase 4 (Car4)-and arise from bulk ECs, as suggested by trajectory analysis. Car4 ECs have extensive cellular projections and are separated from AT1 cells by a limited basement membrane without intervening pericytes. Car4 ECs are specifically lost upon epithelial Vegfa deletion; 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 features. These findings support a signaling role of AT1 cells and shed light on alveologenesis.

| S-EPMC7170573 | biostudies-literature

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung [scRNA-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 | GSE124323 | GEO

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

2020-01-01 | GSE124324 | GEO

Epithelial Vegfa specifies a distinct endothelial population in the mouse lung

Project description:Epithelial Vegfa specifies a distinct endothelial population in the mouse lung

| PRJNA511606 | ENA

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

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

| PRJNA511607 | ENA

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

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

| PRJNA511608 | ENA

Molecular mapping of interstitial lung disease reveals a phenotypically distinct senescent basal epithelial cell population

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-08 | GSE166059 | GEO

The Oxygen Environment at Birth Specifies the Population of Alveolar Epithelial Stem Cells in the Adult Lung.

Project description:Alveolar epithelial type II cells (AEC2) maintain pulmonary homeostasis by producing surfactant, expressing innate immune molecules, and functioning as adult progenitor cells for themselves and alveolar epithelial type I cells (AEC1). How the proper number of alveolar epithelial cells is determined in the adult lung is not well understood. Here, BrdU labeling, genetic lineage tracing, and targeted expression of the anti-oxidant extracellular superoxide dismutase in AEC2s are used to show how the oxygen environment at birth influences postnatal expansion of AEC2s and AEC1s in mice. Birth into low (12%) or high (≥60%) oxygen stimulated expansion of AEC2s through self-renewal and differentiation of the airway Scgb1a1 + lineage. This non-linear or hormesis response to oxygen was specific for the alveolar epithelium because low oxygen stimulated and high oxygen inhibited angiogenesis as defined by changes in V-cadherin and PECAM (CD31). Although genetic lineage tracing studies confirmed adult AEC2s are stem cells for AEC1s, we found no evidence that postnatal growth of AEC1s were derived from self-renewing Sftpc + or the Scbg1a1 + lineage of AEC2s. Taken together, our results show how a non-linear response to oxygen at birth promotes expansion of AEC2s through two distinct lineages. Since neither lineage contributes to the postnatal expansion of AEC1s, the ability of AEC2s to function as stem cells for AEC1s appears to be restricted to the adult lung. Stem Cells 2016;34:1396-1406.

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microRNA expression profiles of distinct human and mouse mammary epithelial cell types

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-02-20 | E-GEOD-67056 | biostudies-arrayexpress

Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin

Project description:This SuperSeries is composed of the SubSeries listed below.

2011-10-07 | GSE32350 | GEO