Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. The highly specialized cell-cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. Dendrin is a poorly characterized cytosolic component of the slit diaphragm in where it interacts with nephrin and Cd2ap. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile and had normal life span.
Wtip- and gadd45a-interacting protein dendrin is not crucial for the development or maintenance of the glomerular filtration barrier.
Age, Specimen part
View SamplesPlatelet-derived growth factor-C (PDGF-C) is one of three known ligands for the tyrosine kinase receptor PDGFR. Analysis of Pdgfc null mice has demonstrated roles for PDGF-C in palate closure and the formation of cerebral ventricles, but redundancy with other PDGFR ligands might hide additional functions. In search of further developmental roles for PDGF-C, we generated mice that were double mutants for Pdgfc -/- and Pdgfra GFP/+. These mice display a range of severe phenotypes including cerebellar malformation, neuronal over-migration in the cerebral cortex, spina bifida and lung emphysema. We focused our analysis on the central nervous system (CNS), where PDGF-C was identified as a critical factor for the formation of meninges and assembly of the glia limitans basement membrane.
A role for PDGF-C/PDGFRα signaling in the formation of the meningeal basement membranes surrounding the cerebral cortex.
Specimen part
View SamplesLittle is known about the pan-microvascular transcriptome, particularly considering gene transcripts and their encoded proteins that can be considered as vascular-selective in their expression.
Identification of a core set of 58 gene transcripts with broad and specific expression in the microvasculature.
No sample metadata fields
View SamplesAdipocyte precursor cells were treated with Pdgfa during 1 or 2 hours in vitro to identify early changes in transciprion in response to treatment. This experiment supports the evidence that Pdgfa induces proliferation and maintenance of adipocyte stem cells. Overall design: Adipocyte precursor cells were isolated by FACS and treated with 30ng/ml of recombinant mouse Pdgfa for 1 or 2 hours.
Skin Adipocyte Stem Cell Self-Renewal Is Regulated by a PDGFA/AKT-Signaling Axis.
Sex, Age, Specimen part, Cell line, Subject
View SamplesVascular smooth muscle cells (VSMC) are important for contraction, blood flow distribution and regulation of blood vessel diameter, but to what extent they contribute to the integrity of blood vessels and blood-brain barrier function is less well understood. In this report, we explored the impact of the progressive loss of VSMC in the Notch3-/- mouse on blood vessel integrity in the central nervous system
Notch3 is necessary for blood vessel integrity in the central nervous system.
Age, Specimen part
View SamplesThe pathogenic mechanisms of common kidney glomerular diseases, including the vast majority of cases of proteinuria, remain unknown.
Glomerular transcriptome changes associated with lipopolysaccharide-induced proteinuria.
No sample metadata fields
View SamplesIgA nephropathy (IgAN) is the most common glomerulonephritis in the world. The disease is characterized by galactose deficient IgA (gd-IgA) in the circulation forming immune complexes. The complexes are deposited in the glomerular mesangium leading to inflammation and loss of renal function, but the pathophysiology of the disease is still not fully understood. Using an integrated global transcriptomic and proteomic profiling approach we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsies from patients with IgAN. The influence of galactose deficient IgA (gd-IgA) on mesangial cells was investigated by proteomic profiling. By utilizing the previous published literature curated glomerular cell type-specific genes, we found that mesangial cells and their positive standard genes play a more dominant role in IgAN comparing to the podocyte standard genes. Additionally, the patient clinical parameters (serum creatinine values and estimated glomerular filtration rate - eGFR) significantly correlate with z-scores derived from expression profile of mesangial cell positive standard genes. 22 common pathways were identified both from in vivo microarray data and in vitro mesangial cell mass spectrometry data and the main part was inflammatory pathways. The correlation between clinical data and mesangial standard genes allows for a better understanding of the onset of IgAN. The genes, proteins and their corresponding pathways identified in this paper give us novel insights into the pathophysiological mechanisms leading to progression of IgAN.
Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy.
Specimen part
View SamplesPurpose:To take a comprehensive effort in characterizing the brain vasculature gene expression upon hyperglycemia. Methods: We extracted mRNA from brain microvasculature fragments isolated from a genetic mouse model of hyperglycemia (Ins2-AKITA) and WT mice and analyzed their transcriptome with RNA sequencing The samples were sequenced on an Illumina HiSeq 2500 sequencer at the SNP&SEQ sequencing facility (Science for Life laboratory (SciLifeLab), Uppsala sequencing node). The reads were aligned to the Ensembl mouse gene assembly (NCBIM37) using Tophat2 software (version 2.0.4). The duplicated reads were removed using the picard tool (version 1.92). To identify the genes significantly enriched in the pericyte samples as compared with microvascular samples, statistical tests were performed using the Cufflinks tool (version 2.2.1) Results: Twenty-three genes were significantly regulated in mutant when compared to WT (False Discovery Rate < 0.05) Overall design: The microvascular RNA from two male heterozygous Ins2-AKITA mice and three littermate wild-type controls were processed and sequenced on the Illumina HiSeq 2500 platform in the sequencing facility in Uppsala University.
Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier.
Sex, Specimen part, Subject
View SamplesBy analyzing 250 astrocyte single cell transcriptomes from adult brain, we provide gene expresssion profile of brain astrocyte Overall design: We chose adult mice about 3 months old and analysed single cells in the brain. We chose a methodology based on fluorescence-activated cell sorting (FACS) into 384-well plates followed by the SmartSeq2 methodology.
Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types.
Specimen part, Cell line, Subject
View SamplesAnalysis of sol2 mutant. SOL2 protein is a receptor-like kinase
The receptor-like kinase SOL2 mediates CLE signaling in Arabidopsis.
No sample metadata fields
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