Single-cell RNAseq analysis of pericyte-deficient endothelium
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ABSTRACT:
PROVIDER: PRJNA608967 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We applied scRNAseq analysis to investigate how the brain mural cell deficiency established in Pdgfb ret/ret mice affects the endothelial cell phenotype.
2020-12-21 | GSE146007 | GEO
Project description:The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB. The brain microvascular fragments were isolated from mice with different genotypes, each represented by 3-4 biological replicates. Genotypes 1-2: Platelet derived growth factor-B (PDGF-B) retention-motif knockout (pdgfbret/ret) represent the pericyte-deficient situation, and the heterozygous mice (pdgfbret/+) are used as controls. Genotypes 3-4: Hypomorphic PDGF-B mutants that rescue pdgfb-/- null mice, in which a one copy of a conditionally silent human PDGF-B transgene targeted to the Rosa 26 locus (R26P) is turned on by endothelial-specific expression of Cre recombinase. In this data set these mice are named as Tie2Cre, R26P+/0, pdgfb-/- (representing the pericyte-deficient situation). Mice wt for pdgfb (pdgfb+/+) and carrying one silent copy of R26P (R26P+/0), are used as controls. Genotype 5: Adult Notch3+/+ wildtype (WT).
2010-10-21 | E-GEOD-15892 | biostudies-arrayexpress
Project description:Pancreatic Epithelial Single Cell RNAseq in OGT-deficient cells
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Project description:Single Cell RNAseq from IL6R deficient patient and healthy parent
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Project description:Proteomics analysis can reveal the differences of protein expression between mural cells (known as pericytes) from normal adjacent tissues (NPC) and tumors (TPC), implying the effectiveness of pericyte to tumor.
2021-08-24 | PXD026963 | Pride
Project description:Brain pericytes are critical for regulating endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. How the developmental acquisition of pericytes to naked endothelium is regulated, is largely unknown, but is relevant to disorders where vessels are poorly stabilized. Although pericytes are derived from neural crest and mesoderm, brain pericytes from both origins are currently indistinguishable; the genetic pathways leading to a convergent pericyte phenotype are unknown. We show here that a precursor population expressing the transcription factor nkx3.1 with origins in both NCC and mesoderm, develops into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1, foxf2a, and cxcl12b -expressing pericyte precursor population is present around the cxcr4 expressing basilar artery, and that these cells later spread throughout the brain. Cxcl12b- Cxcr4 signaling is required for pericyte attachment and differentiation but not for later pericyte development. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number. Thus, we have defined an undescribed population of pericyte precursors and identified genes critical for their differentiation.
2024-02-25 | GSE232163 | GEO
Project description:The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.
2010-10-21 | GSE15892 | GEO
Project description:Background: Pericytes regulate vessel stabilization and function and their loss is associated with diseases such as diabetic retinopathy or cancer. Despite their physiological importance, pericyte function and molecular regulation during angiogenesis remain poorly understood. Methods: To decipher the transcriptomic programs of pericytes during angiogenesis, we crossed the Pdgfrb(BAC)-CreERT2 into the RiboTagflox/flox mice. Pericyte morphological changes were assessed in mural cell-specific R26-mTmG reporter mice, in which low doses of tamoxifen allowed labeling of single cell pericytes at high resolution. To study the role of phosphoinositide 3-kinase (PI3K) signaling in pericyte biology during angiogenesis, we used genetic mouse models which allow selective inactivation of PI3Kα and PI3Kβ isoforms and their negative regulator PTEN (phosphate and tensin homologue deleted on chromosome ten, PTEN) in mural cells. Results: At the onset of angiogenesis, pericytes exhibit molecular traits of cell proliferation and activated PI3K signaling, whereas during vascular remodeling pericytes upregulate genes involved in mature pericyte cell function, together with a remarkable decrease in PI3K signaling. Immature pericytes showed stellate shape and high proliferation, and mature pericytes were quiescent and elongated. Unexpectedly, we demonstrate that the PI3Kβ, but not PI3Kα, regulates pericyte proliferation and maturation during vessel formation. Genetic PI3Kβ inactivation in pericytes triggered early pericyte maturation. Conversely, unleashing PI3K signaling by means of PTEN deletion delayed pericyte maturation. Pericyte maturation was necessary to undergo vessel remodeling during angiogenesis. Conclusions: Our results identify new molecular and morphological traits associated to pericyte maturation and uncover PI3Kβ activity as a checkpoint to ensure appropriate vessel formation. In turn, our results may open new therapeutic opportunities to regulate angiogenesis in pathological processes through the manipulation of pericyte PI3Kβ activity.
2020-06-03 | GSE131534 | GEO
Project description:Brain pericytes are critical for regulating endothelial barrier function and activity, thus ensuring adequate blood flow to the brain. How the developmental acquisition of pericytes to naked endothelium is regulated, is largely unknown, but is relevant to disorders where vessels are poorly stabilized. Although pericytes are derived from neural crest and mesoderm, brain pericytes from both origins are currently indistinguishable; the genetic pathways leading to a convergent pericyte phenotype are unknown. We show here that a precursor population expressing the transcription factor nkx3.1 with origins in both NCC and mesoderm, develops into brain pericytes. We identify the gene signature of these precursors and show that an nkx3.1, foxf2a, and cxcl12b -expressing pericyte precursor population is present around the cxcr4 expressing basilar artery, and that these cells later spread throughout the brain. Cxcl12b- Cxcr4 signaling is required for pericyte attachment and differentiation but not for later pericyte development. Further, both nkx3.1 and cxcl12b are necessary and sufficient in regulating pericyte number. Thus, we have defined an undescribed population of pericyte precursors and identified genes critical for their differentiation.
2024-02-25 | GSE232762 | GEO
Project description:Single Cell RNAseq was performed to identify cell types and upstream regulators in pancreatic epithelial cells with or without OGT.
2020-03-23 | GSE131134 | GEO