Modulation of inflammatory responses in mouse models of pericyte-depletion retinopathy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1260457 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33473150.fastq.gz | Fastqsanger.gz | |||
| SRR33473151.fastq.gz | Fastqsanger.gz | |||
| SRR33473152.fastq.gz | Fastqsanger.gz | |||
| SRR33473153.fastq.gz | Fastqsanger.gz | |||
| SRR33473154.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:A major feature of diabetic retinopathy is pericyte loss. Here, we have utilzed a model of pericyte depletion retinopathy that recapitulates key features of human diabetic retinopathy to study the cellular and molecular components of the diease and response to immunomodulation with minocylcine. Pericyte depletion was achieved via injection of a rat anti-mouse PDGFRB mAb at Postnatal day 1 (P1) in C57BL6/J WT mice. Treatment with minocyline begaun at P5, daily until P27, and retinas analysed from P28 mice. Transcriptomic analyses identifies signature pathways in pericyt-depletion retinopathy and response to minoccyline
2025-05-26 | GSE296651 | 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:Pericytes confer vascular stability in the retina, and the loss of pericytes can cause the blood-retina barrier breakdown seen in diabetic retinopathy. To identify endothelial-specific genes expressed in pericyte-deprived retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice treated with neutralizing antibody against PDGFRb (APB5) and performed gene expression profiling using DNA microarray. To find out endothelial-specific genes associated with the loss of pericyte coverage, the comparison of microarray data was carried out between retinal endothelial cells (data from GSE27238) and APB5-treated retinal endothelial cells.
2017-01-01 | GSE86819 | GEO
Project description:Circular RNAs (circRNAs) are generated by back-splicing and control cellular signaling and phenotypes. Pericytes stabilize the capillary structure and play an important role in the formation and maintenance of new blood vessels. Here, we characterized hypoxia-regulated circRNAs in human pericytes and showed that circPLOD2 is induced by hypoxia and regulates pericyte functions. Silencing of circPLOD2 increased pericyte proliferation, endothelial-pericyte interactions and tube formation. Transcriptional profiling of circPLOD2-depleted cells and epigenomic analyses revealed widespread changes in gene expression and identified the regulation of the transcription factor KLF4 as a key effector of these changes. Importantly, overexpression of KLF4 was sufficient to reverse the effects on pericyte proliferation and endothelial-pericyte interactions observed after circPLOD2 depletion. Together, these data reveal a novel function of circPLOD2 in the control of pericyte proliferation and capillary formation and show that circPLOD2-mediated regulation of KLF4 significantly contributes to the transcriptional response to hypoxia.
2023-06-19 | GSE219237 | GEO
Project description:Photoreceptor survival in CEP290-retinopathy by Reserpine involves modulation of proteostasis
| PRJNA853053 | ENA
Project description:Pathologic ocular angiogenesis is a common cause of blindness in proliferative retinopathy. Small non-coding RNAs (sncRNAs) play critical roles in normal development and diseases, and their function in eye diseases and angiogenesis are increasingly recognized. In the present study, we aimed to identify the function and therapeutic potential of sncRNAs in retinopathy. We used microarray to analyze the retinal expression profile of sncRNAs in a mouse oxygen-induced retinopathy (OIR) model that mimic human proliferative retinopathy.
2017-02-10 | GSE84303 | GEO
Project description:The efficacy of T cell-based immunotherapies is limited by the immune-suppressive tumor environment mediated by hypoxia, arising from dysfunctional blood vessels. Normalizing the tumor vascular bed can translate into an immune-supportive microenvironment. Here, we show that targeting pericytes to achieve durable vessel normalization can improve immunotherapy outcomes. Specifically, we identified regulator of G protein signaling 5 (RGS5) as a master regulator of tumor pericyte differentiation. Loss of RGS5 function changes the tumor microenvironment by inducing pericyte quiescence and maturity via Rho kinase activation and expression of contractile proteins. The mature pericyte state affords highly sustained vascular changes, which profoundly facilitates anti-tumor immune activity. Importantly, we show that selective low dose therapeutics can induce pericyte maturity and contractility, which mimics genetic RGS5 loss in both mouse and human tumors. Low dose drug therapy durably changes the tumor microenvironment without inducing adaptive resistance, rendering malignant cells more sensitive to immunotherapies. Our findings create a new approach with highly translatable opportunities to improve the outcomes of immune combination therapies.
2024-08-23 | GSE271508 | GEO
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:Pericytes are intrinsic components of vessels that regulate vascular stability and permeability. Aberrant vascularization is a hallmark of cancer, although the contribution of pericytes to this process is poorly understood. Here, we undertook a combined computational and experimental strategy to identify the molecular reprogramming of prostate pericytes during cancer pathogenesis and progression. Analysis of human prostate cancer and murine mouse models showed that prostate tumors exhibit a disequilibrium between endothelial and pericyte content with prognostic potential. Deeper molecular analysis revealed that there is no overt loss of pericytes in prostate tumors, but rather a disfunction that is concomitant with altered expression of a subset of cellular markers. We translate this finding into a simplified signature that discriminates pericyte abundance versus function. Leveraging single-cell RNA sequencing data, we find that TGFβ governs the molecular changes that underlie pericyte disfunction in tumors. This mechanism is associated with reduced pericyte contractility, enlargement of vascular lumen and increased permeability in prostate cancer. Altogether, this study revisits the paradigm of reduced number of pericyte in favor of their disfunction in tumors, and the importance of paracrine signaling in this process.
2025-10-03 | GSE278801 | GEO
Project description:Progenitor cell combination normalizes retinal vascular development by enhancing pericyte ensheathment in the oxygen-induced retinopathy (OIR) model
| PRJNA560255 | ENA