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Endothelial Pd1 orchestrates cerebrovasculature homeostasis and oligodendrogenesis during brain development

ABSTRACT: Purpose: To explore further into the mechanisms by which endothelial PD1 controls cerebrovascular development and oligodendrogenesis, we employed RNA-seq to examine genome-wide alterations in endothelial cells from P0 conditional PD1 knockout mice, comparing them with their wild-type littermates. Methods: mRNA was extracted from P0 isolated endothelial cells of Pd1fl/fl and Pd1cKO-Tie2 mice, and the quality and quantity were assessed using the Agilent 2100 Bioanalyzer. Subsequently, the mRNA was converted to cDNA and Libraries were prepared. RNA-sequencing was performed on the Illumina HiSeq 2500 platform at Annoroad Genomics. Results: Approximately one thousand transcripts showed differential expression between the Pd11fl/fl and Pd1cKO-Tie2 mice brain endothelial cell, with a fold change ≥2 and p value <0.05.Geneontology analysis of the downregulated genes were enriched in terms related to positive regulation of angiogenesis, positive regulation of vascular endothelial growth factor production and positive regulation of inflammatory response. Concomitantly, upregulated genes were enriched in terms related to endothelial cell migration, sequestering of BMP from receptor via BMP binding and regulation of establishment of blood-brain barrier. These results reflected endothelial PD1 plays vital roles in cortex development. Conclusions: Endothelial PD1 RNA-seq would provide a overall understanding how endothelium-derived PD1regulates vessel development and oligodendrogenesis during brain development

ORGANISM(S): Mus musculus

PROVIDER: GSE267172 | GEO | 2024/05/13

REPOSITORIES: GEO

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Endothelial RNF20 regulates the self-renewal and differentiation of neural precursor cells during embryonic development

Project description:Purpose: To further explore how endothelial RNF20 regulates embryonic neurogenesis, RNA isolated from the endothelial cells of RNF20fl/fl and RNF20cKO-Tie2 brain cortex at E13 was analyzed by RNA-seq to determine the genome-wide changes. Methods: mRNA from E13 isolated endothelial cells of RNF20fl/fl and RNF20cKO-Tie2 mice was extracted. Specifically, Agilent 2100 Bioanalyze was used to quality controlled and quantified. then, mRNA was converted to cDNA and bound the library. RNA-sequencing analysis was used by the Illumina HiSeq 2500 platform in Annoroad Genomics Results: Approximately one thousand transcripts showed differential expression between the RNF20fl/fl and RNF20cKO-Tie2 mice brain cortex, with a fold change ≥2 and p value <0.05. Gene ontology analysis of downregulated genes showed the genes were enriched in terms related to neuron differentiation, cell communication and secretion by cells.Concomitantly, upregulated genes were enriched in terms related to negative regulation of cytokine production and cell development.The results showed that endothelial RNF20 is critical for neurogenesis. Conclusions: Endothelial RNF20 RNA-seq would provide a overall understanding how endothelial RNF20 regulates the self-renewal and differentiation of neural precursor cells during embryonic development

2022-01-07 | GSE192997 | GEO

Role of Pfn-1 phosphorylation in gene expression in glioma-associated endothelial cells

Project description:Analysis of gene expression in glioma-associated endothelial cells in Tie2-Cre,Pfn1fl/fl:Y129F and Pfn1fl/fl:Y129F mice We detected different gene expression patterns in the tumor-associated endothelial cells in Tie2-Cre,Pfn1fl/fl:Y129F and Pfn1fl/fl:Y129F mice

2014-02-25 | GSE55295 | GEO

Role of Pfn-1 phosphorylation in gene expression in glioma-associated endothelial cells

2014-02-25 | E-GEOD-55295 | biostudies-arrayexpress

Endothelial Arid1a Deletion Disrupts the Balance among Angiogenesis, Neurogenesis, and Astrogenesis in the Developing Brain

Project description:Purpose:To gain futher insight into how endothelial Arid1a regulates the angiogenesis, neurogenesis, and astrogenesis,RNA-seq was used to analyze the genome-wide changes resulting from isolated endothelial cells of E15 Arid1a endothelial conditional knockout mice and littermate wild-type. Methods: mRNA from E15 isolated endothelial cells of Arid1afl/fl and Arid1acKO-Tie2 mice was extracted. Specifically, Agilent 2100 Bioanalyze was used to quality controlled and quantified. then, mRNA was converted to cDNA and bound the library. RNA-sequencing analysis was used by the Illumina HiSeq 2500 platform in Annoroad Genomics. Results: Approximately one six thousand transcripts showed differential expression between the Arid1afl/fl and Arid1acKO-Tie2 mice brain cortex, with a fold change ≥2 and p value <0.05.Geneontology analysis of the up-regulated genes showed obvious enrichment of biological processes related to development process and regulation of cell communication.The down-regulated genes exhibited enrichment of biological processes related to cell movement. These results reflected endothelial Arid1a plays a vital role in cortex development. Conclusions: Endothelial Arid1a RNA-seq would provide a overall understanding how endothelial Arid1a regulates the Balance among angiogenesis, neurogenesis, and astrogenesis in the developing Brain

2022-12-21 | GSE221176 | GEO

Endothelial cells mediated by STING signaling regulate oligodendrogenesis and myelination during brain development

Project description:To gain futher insight into how endothelial STING regulates oligodendrogenesis ,RNA-seq was used to analyze the genome-wide changes resulting from isolated endothelial cells of E18 endothelial STING conditional knock out mice and littermate wild-type.mRNA from E18 isolated endothelial cells of wild-type(WT) and STINGf/f;Tie2-cre mice was extracted. Specifically, Agilent 2100 Bioanalyze was used to quality controlled and quantified. then, mRNA was converted to cDNA and bound the library. RNA-sequencing analysis was used by the Illumina HiSeq 2500 platform in Annoroad Genomics

2023-03-25 | GSE227955 | GEO

FACS-array profiling in retinal endothelial cells from living mouse retinas

Project description:Deregulated retinal angiogenesis directly cause vision loss in many ocular diseases, such as diabetic retinopathy and retinopathy of prematurity. To identify endothelial-specific genes expressed in angiogenic retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice and performed gene expression profiling using DNA microarray. To find out genes associated with angiogenesis, comparisons of microarray data were carried out between GFP-negative non-endothelial retinal cells and GFP-positive retinal endothelial cells in angiogenic P8 retina. Eighteen arrays are included. Utilizing fluorescence-activated cell sorting (FACS), we isolated endothelial cells as GFP-positive cells from P8 retina in homozygous Tie2-GFP transgenic mice. GFP-negative cells were served as non-endothelial control. RNA extracts from sorted cells were amplified and then hybridized to Affymetrix MGU74v2 series arrays in triplicate.

2011-04-17 | E-GEOD-27238 | biostudies-arrayexpress

Pd1 regulates proliferation and differentiation of neural progenitors during brain development

Project description:To gain a total insight into how Pd1 regulates embryonic neurogenesis, RNA-seq was performed to compare the different expressed genes ar E13. Approximately approximately one thousand transcripts showed differential expression between the Pd1fl/fl and Pd1CKO mice brain cortex, with a fold change ≥1.5 and p value <0.05. These results indicated the importance of Pd1 in cortical development. RNA-seq based transcriptome characterization would provide a global understanding how Pd1 gene contribute to brain cortical development.

2022-07-11 | GSE207712 | GEO

Expression data of E13.5 mouse Blood Brain Barrier and lung endothelial cells

Project description:Following the identification of a critical time window of Blood Brain Barrier formation in the mouse embryo, we aimed to identify genes important for barriergenesis. To this end, we isolated cortical and lung E13.5 endothelial cells and compared expression between the two populations. The working hypothesis was that endothelial cells which are actively building a barrier would have a uniqe pattern of gene expression that would be detectable in comparison to a non-barrier endothelial population that is also active in vasculogenesis. E13.5 Tie2-GFP embryos were micro-dissected for cortex and lungs. Cortex tissue was carefully cleared of the meninges and choroid plexus. FACS purification of GFP positive cells and GeneChip analysis was applied . All material from a single litter (10-13 embryos) was pooled and considered as a biological replicate. n=4 litters.

2014-05-14 | E-GEOD-56777 | biostudies-arrayexpress

The Pitx2:miR-200c/141:noggin pathway regulates BMP signaling and ameloblast differentiation

Project description:The mouse incisor is a remarkable tooth that grows throughout the animalM-bM-^@M-^Ys lifetime. This continuous renewal is fueled by epithelial stem cells that give rise to ameloblasts, which generate enamel, and little is known about the function of specific miRNAs in this process. Here we describe the role of a novel Pitx2:miR-200c/141:Noggin regulatory pathway in dental epithelial cell differentiation. miR-200c repressed noggin, an antagonist of Bmp signaling. Pitx2 expression caused an up-regulation of miR-200c and chromatin immunoprecipitation (ChIP) assays revealed endogenous Pitx2 binding to the miR-200c/141 promoter. A positive feedback loop was discovered between miR-200c and Bmp signaling. miR-200c/141 induced expression of E-cadherin and the dental epithelial cell differentiation marker, amelogenin. In addition, miR-203 expression was activated by endogenous Pitx2 and targeted the Bmp antagonist Bmper to further regulate Bmp signaling. miR-200c/141 knockout mice showed defects in enamel formation with decreased E-cadherin and amelogenin expression and increased noggin expression. Our in vivo and in vitro studies reveal a multistep transcriptional program involving the Pitx2:miR-200c/141:Noggin regulatory pathway that is important in epithelial cell differentiation and tooth development. Lower incisors of 3-5 P0 WT and Pitx2-Cre;Dicer1 cKO mices from same litter were dissected and combined for RNA extraction. Two different litters were analyzed. For mRNA microarray, CodeLink Mouse Whole Genome chips (Applied Microarrays) were used according to manufacturerM-bM-^@M-^Ys instruction (done at Genomics Core of TAMU). miRNA from P0 Lower Incisor ameloblast and cervical loops.

2013-07-09 | E-GEOD-48583 | biostudies-arrayexpress

Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood-brain barrier integrity

Project description:Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional EphA4f/f/Tie2-Cre and EphA4f/f/VE-Cadherin-CreERT2 knockout (KO) mice, promotes blood-brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury. scRNAseq of capillary-derived KO ECs showed increased differential gene expression of BBB-related junctional and actin cytoskeletal regulators, namely, A-kinase anchor protein 12, Akap12, whose presence at Tie2 clustering domains is enhanced in KO microvessels. Transcript and protein analysis of CCI-injured whole cortical tissue or cortical-derived ECs suggests EphA4 limits the expression of Cldn5, Akt, and Akap12 and promotes Ang2. Blocking the Tie2 receptor using sTie2-Fc, attenuated BBB and tissue protection and reversed Akap12 mRNA and protein levels in KO compared to WT cortical-derived ECs. Conversely, direct stimulation of Tie2 using Vasculotide, an angiopoietin-1 memetic peptide, phenocopied the neuroprotection. Finally, we report a noteworthy rise in soluble Ang2 in the sera of individuals with acute TBI, highlighting its promising role as a vascular biomarker for early detection of BBB disruption. Overall, we describe a novel contribution of the axon guidance molecule, EphA4, in mediating TBI microvascular dysfunction through negative regulation of Tie2/Akap12 signaling.

2023-09-24 | GSE240430 | GEO

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