Endocapillary proliferation is associated with higher risk of progressive disease in IgAN. To better understand molecular pathways involved in the development of endocapillary proliferation and to identify novel specific therapeutic targets, we evaluated the glomerular transcriptome of microdissected kidney biopsies from 22 patients with IgAN. Endocapillary proliferation was defined according to the Oxford scoring system by 3 nephropathologists. We analyzed mRNA expression using microarrays and identified transcripts differentially expressed in patients with endocapillary proliferation. Next, we employed both transcription factor analysis and in silico drug screening and confirmed that the endocapillary proliferation transcriptome is significantly enriched with pathways modulated by corticosteroid exposure. With this approach we also identified novel therapeutic targets and bioactive small molecules that may be considered for therapeutic trials for treatment of IgAN.
The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.
Specimen part
View SamplesGene expression, histone modification, DNA methylation, and DNA hydroxymethylation from normal, cirrhotic, and HCC livers Overall design: 10 total samples (2 normal, 4 cirrhosis, 4 HCC). Cirrhosis and HCC are from the same four patients.
Integrating the Epigenome to Identify Drivers of Hepatocellular Carcinoma.
No sample metadata fields
View SamplesGene expression profiles of WT (wild type) and CCM-1, -2, and -3 KD (knockdown of krit1, ccm2 and pdcd10 genes) cells under 2D (Matrigel-coated plastic) and 3D (Matrigel) conditions. Deep sequencing of RNA was performed for cells at the initial (2hrs) and later (6hrs) stages of EC tubule formation. Overall design: Comparative analysis of gene expression of healthy and diseased cells in the tube formation assay
Biomechanics of Endothelial Tubule Formation Differentially Modulated by Cerebral Cavernous Malformation Proteins.
Cell line, Subject
View SamplesDnmt3a catalyzes DNA methylation of gDNA, which contributes to the transriptional regulations of genes and genomic stability.
Methylation-independent repression of Dnmt3b contributes to oncogenic activity of Dnmt3a in mouse MYC-induced T-cell lymphomagenesis.
Age, Specimen part
View SamplesPreparation of exosomes isolated from semen contain a substantial amount of RNA, mostly from 20 to 100 nucleotides in length. We sequenced separately 20-40 and 40-100 nucleotide fractions of RNA from exosomes isolated from semenal fluid from six healthy donors. We found various classes of small non-coding RNA, including mature microRNA and piwi-RNA, as well as abundant Y RNAs and tRNAs present in both full length and fragmented forms. Specific RNAs were consistently present in all donors. For example, fifteen (of ~2,600 known) microRNAs constituted over 80% of mature microRNA in SE. Additionally, tRNA fragments were strongly enriched for 5’-ends of 18-19 or 30-34 nucleotides in length. Overall design: Size-fractionated small RNA profiles from exosomes isolated from the seminal fluid of six healthy donors
Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions.
No sample metadata fields
View SamplesLung development and function arises from the interactions between diverse cell types and lineages. Using single cell RNA-seq we characterize the cellular composition of the lung during development and identify vast dynamics in both the composition of cells and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, ILC and basophils. Using IL33-receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and GM-CSF, characterized by unique signaling of cytokines and growth factors important for stromal, epithelial and myeloid cell fates. Antibody depletion strategies, diphtheria toxin–mediated selective depletion of basophils, and co-culture studies, show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole tissue cell interaction analysis on the single cell level can broaden our understanding of cellular networks in health and disease. Overall design: Transcriptional profiling of single cells from the different timepoints of lung development, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500 metadata.txt: Meta data file associating each single cell with its amplification batch and index sorting readouts
Lung Single-Cell Signaling Interaction Map Reveals Basophil Role in Macrophage Imprinting.
Specimen part, Cell line, Treatment, Subject
View SamplesTREM-2 has been described to be a phagocytic receptor. We assessed the influence of TREM-2 on gene expression in alveolar macrophages (AM)
The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia.
Specimen part
View SamplesIn MTN-007, a phase 1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies taken at baseline, after one application or after seven daily applications (15 subjects/arm). Experiments were repeated using primary vaginal epithelial cells from four healthy women.
Mucosal effects of tenofovir 1% gel.
Specimen part, Treatment
View SamplesIn MTN-007, a phase 1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies taken at baseline, after one application or after seven daily applications (15 subjects/arm). Experiments were repeated using primary vaginal epithelial cells from four healthy women.
Mucosal effects of tenofovir 1% gel.
Sex, Specimen part, Subject
View SamplesDnmt3b is a DNA methytransferase which is an enzyme that methylated genomic DNA which contributes to genomic stability and transcriptional regulation.
Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis.
Specimen part
View Samples