Profiling of vascular organoid endothelial cells and pericytes from iPS cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA482245 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7549230.fastq.gz | Fastqsanger.gz | |||
| SRR7549240.fastq.gz | Fastqsanger.gz | |||
| SRR7549250.fastq.gz | Fastqsanger.gz | |||
| SRR7549231.fastq.gz | Fastqsanger.gz | |||
| SRR7549241.fastq.gz | Fastqsanger.gz |
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Project description:Pericytes/vascular smooth muscle cells (VSMCs), regulated by platelet-derived growth factor receptor β (PDGFRβ) signaling, play important roles in endothelial survival and vascular stability. Here we report that treatment with imatinib, an inhibitor of PDGFRβ, led to significant tumor growth impairment associated with increased apoptosis in human lymphoma xenografts including Farage, Karpas422 and OCI-Ly7 in SCID mice. Confocal analysis of the tumor tissue showed decreased microvessel density, decreased vascular flow, and increased vascular leak in the imatinib-treated cohorts. Imatinib targeted tumor-associated PDGFRβ+ pericytes in vivo by inducing apoptosis and disruption of the PDGFRβ+ perivascular network, and PDGFRβ+ VSMC in vitro by inhibition of proliferation. FACS analysis of mononuclear cell suspension of tumor tissues revealed decreased mature pericytes and endothelial cells, as well as their progenitors with imatinib treatment. Compared to imatinib, treatment with anti-PDGFRβ monoclonal antibody partially inhibited the growth of Farage lymphomas. Lastly, microarray analysis of differentially expressed genes in PDGFRβ+ VSMC following imatinib treatment showed significant down-regulation of genes implicated in proliferation, survival and angiogenesis, including those within PI3K/AKT and MAPK/ERK1/2 pathways downstream of PDGFRβ signaling. Taken together, targeting PDGFRβ+ pericytes in lymphoma presents a novel and complementary target to endothelial cells for efficacious antiangiogenic therapy. PDGFRb+ murine vascular smooth muscle cells (VSMCs) were treated in 10 uM imatinib for 24 or 48 hours. Gene expression changes in response to imatinib treatment were examined using NimbleGen MM8_60mer gene expression microarrays by comparing expression patterns at 24- and 48-hours treatment to the baseline level (0 hours).
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Project description:We have established a vascular organoid culture system with self-assembled endothelial networks that are covered by a basement membrane and pericytes. CD31+ endothelial cells, and CD140b positive pericytes were FACS sorted and RNA-seq was performed.
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Project description:Pericytes/vascular smooth muscle cells (VSMCs), regulated by platelet-derived growth factor receptor β (PDGFRβ) signaling, play important roles in endothelial survival and vascular stability. Here we report that treatment with imatinib, an inhibitor of PDGFRβ, led to significant tumor growth impairment associated with increased apoptosis in human lymphoma xenografts including Farage, Karpas422 and OCI-Ly7 in SCID mice. Confocal analysis of the tumor tissue showed decreased microvessel density, decreased vascular flow, and increased vascular leak in the imatinib-treated cohorts. Imatinib targeted tumor-associated PDGFRβ+ pericytes in vivo by inducing apoptosis and disruption of the PDGFRβ+ perivascular network, and PDGFRβ+ VSMC in vitro by inhibition of proliferation. FACS analysis of mononuclear cell suspension of tumor tissues revealed decreased mature pericytes and endothelial cells, as well as their progenitors with imatinib treatment. Compared to imatinib, treatment with anti-PDGFRβ monoclonal antibody partially inhibited the growth of Farage lymphomas. Lastly, microarray analysis of differentially expressed genes in PDGFRβ+ VSMC following imatinib treatment showed significant down-regulation of genes implicated in proliferation, survival and angiogenesis, including those within PI3K/AKT and MAPK/ERK1/2 pathways downstream of PDGFRβ signaling. Taken together, targeting PDGFRβ+ pericytes in lymphoma presents a novel and complementary target to endothelial cells for efficacious antiangiogenic therapy.
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Project description:Pericytes serve critical roles including stabilization of neovessels during vasculogenesis and angiogenesis. In larger blood vessels such as the aorta, pericytes are associated with the vasa vasorum, a microvascular network within the outer layer of the adventitia. Using pericytes from both normal and aneurysmal human aorta, this study sought to determine the influence of spheroid culture conditions on aortic vasa vasorum-associated pericyte phenotype and function. Here, we reveal the remarkable plasticity of pericytes as three-dimensional spheroid-based culture of human aorta-derived pericytes, which yields an organoid that promotes pro-angiogenic pathways. The marker profile of pericyte-generated organoids serves as an inducible and importantly, reversible phenotypic signature of pericyte activation. Pericytes from human aneurysm exhibit diminished pro-angiogenic activation and persist in a quiescent, hypercontractile state in organoid culture, thus pointing to a potential to uncover new pathophysiology of human aortic disease.
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Project description:Age-related macular degeneration (AMD) is a prevalent neuroinflammation condition and the leading cause of irreversible blindness among the elderly population. Smoking significantly increases AMD risk, yet the mechanisms remain unclear. Here, we investigated the role of Sema4D-PlexinB1 axis in the progression of AMD, in which Sema4D-PlexinB1 is highly activated by smoking. Using patient-derived samples and mouse models, we discovered that smoking increased the presence of Sema4D on the surface of CD8+ T cells that migrated into the choroidal neovascularization (CNV) lesion via CXCL12-CXCR4 axis and interacted with its receptor PlexinB1 on choroidal pericytes. This led to ROR2-mediated PlexinB1 phosphorylation and pericytes activation, hence disrupted vascular homeostasis and promoted neovascularization. Inhibition of Sema4D reduced CNV and improved the benefit of anti-VEGF treatment. In conclusion, this study unveils the molecular mechanisms through which smoking exacerbates AMD pathology, and presents a potential therapeutic strategy by targeting Sema4D to augment current AMD treatments.
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Project description:The objective of this array was to determine the global gene expression profile of human placental pericytes for comparison with other publicly available arrays of pericytes and mesenchymal stromal cells isolated from various human tissues. Pericytes are critical cellular components of the microvasculature that play a major role in vascular development and pathologies, yet their study has been hindered by lack of a standardized method for their isolation and growth. Here we report a method for culturing human pericytes from a readily available tissue source, placenta, and provide a thorough characterization of resultant cell populations. We developed an optimized protocol for obtaining pericytes by outgrowth from microvessel fragments recovered after enzymatic digestion of human placental tissue. We characterized outgrowth populations by immunostaining, by gene expression analysis, and by functional evaluation of cells implanted in vivo. Our approach yields human pericytes that may be serially expanded in culture and that uniformly express the cellular markers NG2, CD90, CD146, α-SMA, and PDGFR-β, but lack markers of smooth muscle cells, endothelial cells, and leukocytes. When co-implanted with human endothelial cells into C.B-17 SCID/bg mice, human pericytes invest and stabilize developing human endothelial cell-lined microvessels. We conclude that our method for culturing pericytes from human placenta results in the expansion of functional pericytes that may be used to study a variety of questions related to vascular biology. Total RNA from three different pericyte isolations at subculture 1 was collected and examined for relative gene expression.
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