Epithelial Vegfa specifies a distinct endothelial population in the mouse lung [scRNA-seq]
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PROVIDER: PRJNA511607 | ENA |
REPOSITORIES: ENA
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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
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
Project description:Epithelial Vegfa specifies a distinct endothelial population in the mouse lung
| PRJNA511606 | ENA
Project description:Epithelial Vegfa specifies a distinct endothelial population in the mouse lung [bulk RNA-seq]
| PRJNA511608 | ENA
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-01-01 | GSE124325 | GEO
Project description:Purpose: We report expression of a new Cas13 enzyme in retinal cells and evaluate its efficacy in targeting the VEGFA mRNA to establish safety and efficacy of the enzyme got anti-VEGFA therapy. Methods: Three retinal organoids were cultured and treated, (1) Untreated, (2) AAV2.7m8.Cas13bt3.VEGFA.sgRNA, (3) AAV2.7m8.Cas13bt3.NTsgRNA. Single-cell RNA sequencing was performed to determine expression of Cas13bt3 across retinal cell types, and the corresponding VEGFA mRNA expression. Results: All retinal cell showed observable transduction and RPE cells were found most susceptible to infection, while bipolar cells had the least infection rate. Significant silencing of VEGFA was observed in RPE cells. Conclusions: AAV2.7m8 can be used for retina-wide transduction, and Cas13bt3 may be a potential new tool for control of VEGFA.
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Project description:The bivalent domain at promoter region is a unique epigenetic feature poised for activation or repression during cell differentiation in embryonic stem cell. However, the function of bivalent domains in already differentiated cells remains exclusive. By profiling the epigenetic landscape of endothelial cells during VEGFA stimulation, we discovered that bivalent domains are widespread in endothelial cells and preferentially marked genes responsive to VEGFA. The bivalent domains responsive to VEGFA have more permissive chromatin environment comparing to other bivalent domains. The initial activation of bivalent genes depends on RNAPII pausing release induced by EZH1 rather than removal of H3K27me3. The later suppression of bivalent gene expression depended on KDM5A recruitment by its interaction with PRC2. Importantly, EZH1 promoted both in vitro and in vivo angiogenesis by upregulating EGR3, whereas KDM5A dampened angiogenesis. Collectively, this study demonstrated a novel dual function of bivalent domains in endothelial cells to control VEGF responsiveness and angiogenesis.
2020-10-17 | GSE139077 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE32348: Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin (mRNA) GSE32349: Methylation specifies distinct estrogen-induced binding site repertoires of CBP to chromatin (ChIP-Seq) Refer to individual Series
2011-10-06 | E-GEOD-32350 | biostudies-arrayexpress
Project description:Metastasis is responsible for the majority of cancer-related deaths1. Although single-cell RNA sequencing (scRNA-seq) has revealed considerable heterogeneity among tumor cells, identifying the cellular determinants of metastasis has remained challenging. Here, we analyzed scRNA-seq data of primary human breast tumor biopsies and identified a minority population of immature THY1+/VEGFA+ basal epithelial cells that display angiogenic features and are marked by the expression of the oncogene, LMO2. Higher levels of LMO2+ basal cells in human breast tumors correlated with endothelial content and predicted poor distant recurrence-free survival. Using MMTV-PyMT/Lmo2CreERT2 mice, we demonstrate that Lmo2 lineage-traced cells integrate into the vasculature and metastasize to the lung. In human breast tumors, knockdown of LMO2 reduced lung metastasis by affecting multiple steps required for intravasation, leading to a reduced frequency of circulating tumor cells. Mechanistically, we find that LMO2 is a binding partner of STAT3 and is required for STAT3 activation in the presence of the inflammatory cytokines, TNFα and IL6. Collectively, our study identifies a population of metastasis-initiating cells with angiogenic features and establishes the LMO2-STAT3 signaling axis as a therapeutic target in breast cancer metastasis.
2023-10-08 | GSE159284 | GEO