Cholesterol is one of the key molecules in mammals and the most striking examples of its deficiency are the inborn errors of cholesterol biosynthesis that manifest in severe whole body phenotypes. Liver, the principal site of cholesterol homeostasis, has rarely been investigated in these defects. We thus focused on the hepatocyte-specific deletion of lanosterol 14-demethylase (CYP51) catalyzing the rate-limiting step in the post-squalene part of cholesterol synthesis.
Lessons from hepatocyte-specific Cyp51 knockout mice: impaired cholesterol synthesis leads to oval cell-driven liver injury.
Sex, Specimen part, Treatment
View SamplesAccute stretch and tachycardia are capable of inducing pathological excitation transcription coupling - an early invent before structural cardiac remodeling which transitions to heart failure. The sodium calcium exchanger is a key player in maintaining calcium homeostasis and is implicated in pathological signaling during heart failure.
The role of stretch, tachycardia and sodium-calcium exchanger in induction of early cardiac remodelling.
Specimen part, Treatment
View SamplesThe process of early development of mammals is subtly and accurately controlled by the regulation networks of embryo cells. Time course expression data measured at different stages during early embryo development process can give us valuable information by revealing the dynamic expression patterns of genes in genome wide scale. In this study, bovine embryo expression data were generated at oocyte, one cell stage, two cell stage, four cell stage, eight cell stage, sixteen cell stage, morula, and blastocyst; Human embryo expression data were generated at one cell stage, two cell stage, four cell stage, eight cell stage, morula, and blastocyst; Mouse embryo expression data were generated at one cell stage, two cell stage, four cell stage, eight cell stage, morula, and blastocyst.
Rewirable gene regulatory networks in the preimplantation embryonic development of three mammalian species.
No sample metadata fields
View SamplesBACKGROUND: Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4+ T-cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4+ T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4+ T-cells co-cultured with CD11c+ myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post-integration latent infection in resting CD4+ T-cells, and examined potential cell interactions that may be involved using RNA-seq. RESULTS: mDC (CD1c+), SLAN+ DC and CD14+ monocytes were most efficient in stimulating proliferation of CD4+ T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4+ T-cells following HIV-1 infection of APC-T-cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non-proliferating CD4+ T-cells. Gene expression analysis, comparing the mDC, SLAN+ DC and CD14+ monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4+ T-cells via cell-cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene). CONCLUSIONS: APC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14+ monocytes, were able to efficiently induce post-integration HIV-1 latency in non-proliferating CD4+ T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1 latency may provide novel targets to eliminate HIV latency. Overall design: mRNA profiles of sorted, pure antigen presenting cells including, CD1c+ myleoid dendirtic cells (mDC), SLAN+ mDC, CD14+ monocytes and plasmacytoid DC (pDC), were generated using next generation sequencing in triplicate, using Illumina Illumina Hiseq 2000.
The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4(+) T-cells.
No sample metadata fields
View SamplesThe Dahl salt-sensitive (S) rat model develops chronic hypertensive disease when fed a high salt diet that ultimately results in renal and heart failure, as well as prevalent cerebrovascular pathologies. Phenotypic changes in the cerebral vasculature are preceded by changes in gene expression, and evidence supports a role for extracellular signal-regulated kinase 1/2 (ERK1/2) in vascular cell proliferation, yet little is known regarding ERK1/2 regulated gene transcription in cerebrovascular smooth muscle during hypertension. Findings presented here support the hypothesis that salt-induced hypertensive disease results in upregulation of ERK1/2 activity and ERK1/2-regulated genes that promote remodeling in cerebral resistance arteries. Dahl S rats were fed either a 0.4% NaCl (low salt, LS) or 8% NaCl (high salt, HS) diet until evidence of left ventricular dysfunction. Gene expression profiling using oligonucleotide array analysis detected a significant fold-change of 1.5 or greater in 133 out of 15,923 genes examined. Mitogen-activated protein kinase (MAPK)-regulated genes were overrepresented and provided a link to genes involved in proliferation and extracellular matrix signaling including plasminogen activator inhibitor I (PAI-1), osteopontin (OPN) and junB. These data suggests that salt induced hypertensive disease promotes hyperplasia and changes in matricellular genes that are likely important in vascular remodeling.
Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB.
Specimen part
View SamplesMany heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the of toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays.
Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line.
No sample metadata fields
View SamplesIn this report, we describe a successful protocol for isolating and expression-profiling live fluorescent- protein-labelled neurons from zebrafish embryos. As a proof-of-principle for this method, we FAC-sorted and RNA-profiled GFP-labelled spinal CiA interneurons and compared the expression profile of these cells to those of post-mitotic spinal neurons in general and to all trunk cells. We show that RNA of sufficient quality and quantity to uncover both expected and novel transcription profiles via Affymetrix microarray analysis can be extracted from 5,700 to 20,000 FAC-sorted cells. As part of this study, we also further confirm the genetic homology of mammalian and zebrafish V1 interneurons, by demonstrating that zebrafish V1 cells (CiAs) express genes that encode for the transcription factors Lhx1a and Lhx5. This protocol for dissociating, sorting and RNA-profiling neurons from organogenesis-stage zebrafish embryos should also be applicable to other developing organs and tissues and potentially other model organisms.
RNA profiling of FAC-sorted neurons from the developing zebrafish spinal cord.
Age, Specimen part
View SamplesHair follicle matrix, outer root sheath, dermal papilla cells and melanocytes and a dermal fraction enriched in fibroblasts were FACS isolated from 4d backskins. Targets from two biological replicates of each were generated and the expression profiles were determined using Affymetrix Mouse Genechip 430A arrays. Comparisons between the sample groups allow the identification of cell-type specific genes.
Molecular dissection of mesenchymal-epithelial interactions in the hair follicle.
No sample metadata fields
View SamplesAnalysis of genes regulated by Maf and donwstream of ErbB2 in P8 Schwann cells
Maf links Neuregulin1 signaling to cholesterol synthesis in myelinating Schwann cells.
Specimen part
View SamplesHuman embryonic stem cells were differentiated into peripheral sensory neurons via the intermediate generation of neural crest like cell (NCC). Using various markers we identified these cells as LTMR. We then analyzed there complete transcriptional profile in comparison to the intermediate neural crest like cells. Overall design: mRNA expression data of human ESC-derived sensory neuron clusters (10-20 cells) and human ESC-derived neural crest like cells (~100 cells) was generated by illumina deep sequencing
PIEZO2 is required for mechanotransduction in human stem cell-derived touch receptors.
No sample metadata fields
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