Transcriptional dysregulation is an early feature of Huntington''s disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD. Overall design: mRNA-seq in wild type and R6/2 cortex and striatum at 8 and 12 weeks.
Targeting H3K4 trimethylation in Huntington disease.
Age, Specimen part, Subject
View SamplesWe performed an RNA Sequencing experiment on dorsal hippocampal tissue from four groups of animals: Baf53b+/- homecage (Baf53b+/- HC); Baf53b+/- behavior (Baf53b+/- Beh); wildtype homecage (WT HC); and wildtype behavior (WT Beh). Homecage animals were sacrificed directly from the animal's cage. Behavior animals were sacrificed thirty minutes following Object Location Memory training. The objective of this study was to examine activity regulated gene expression following a learning event (HC vs Beh) in wildtype and Baf53b+/- mutant mice. Overall design: Examination of gene expression following a learning event in wildtype and Baf53b+/- mutant mice in dorsal hippocampus.
The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory.
Specimen part
View SamplesThe functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34- negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis.
CD34 marks angiogenic tip cells in human vascular endothelial cell cultures.
Specimen part, Subject
View SamplesBackground: The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport proteins and metabolic enzymes, often collectively called intestinal barrier proteins. An important receptor that mediates the effects of dietary lipids on gene expression is the peroxisome proliferator-activated receptor alpha (PPAR), which is abundantly expressed in enterocytes. In this study we examined the effects of acute nutritional activation of PPAR on expression of genes encoding intestinal barrier proteins. To this end we used triacylglycerols composed of identical fatty acids in combination with gene expression profiling in wild-type and PPAR-null mice. Treatment with the synthetic PPAR agonist WY14643 served as reference.
PPARalpha-mediated effects of dietary lipids on intestinal barrier gene expression.
No sample metadata fields
View SamplesPlants often face combinatorial stresses in their natural environment. Here arsenic (As) toxicity was combined with hypoxia (Hpx) in the roots of Arabidopsis thaliana as it often occurs in nature. The present work aimed to explore the effects of single and combined hypoxia and As stress applied at realistic stress levels to hydroponically grown A. thaliana.
Interference between arsenic-induced toxicity and hypoxia.
Specimen part
View SamplesWe report that whole body PRMT7-/- adult mice display a significant reduction in in muscle mass. RNA sequencing was performed to identify potential PRMT7 targets. We found that top canonical pathways affected by the loss of PRMT7 includes cell cycle and senescence. Overall design: RNA was extracted from tibialis anterior muscles harvested from 3 WT and 3 PRMT7 null mice at 8months. RNA sequencing was performed to compare mRNA in skeletal muscles between WT and KO mice.
PRMT7 Preserves Satellite Cell Regenerative Capacity.
Age, Specimen part, Cell line, Subject
View SamplesFindings suggest that PPARalpha plays a decisive role in the development of hypertrophy, affecting the functional outcome of the heart. Unfortunately, information on the nature of PPARalpha-dependent processes in cardiac hypertrophy is fragmentary and incomplete.
Transcriptomic analysis of PPARalpha-dependent alterations during cardiac hypertrophy.
No sample metadata fields
View SamplesThere were two genotypes:
Loss of a callose synthase results in salicylic acid-dependent disease resistance.
No sample metadata fields
View SamplesDiffuse intrinsic pontine glioma (DIPG) is a universally fatal malignancy of the childhood central nervous system, with a median overall survival of 9-11 months. We have previously shown that primary DIPG tissue contains numerous tumor-associated macrophages, and substantial work has demonstrated a significant pathological role for adult glioma-associated macrophages. However, work over the past decade has highlighted many molecular and genomic differences between pediatric and adult glioblastomas (GBM). Thus, we directly compared inflammatory characteristics of DIPG and adult GBM. We found that the leukocyte (CD45+) compartment in primary DIPG tissue samples is predominantly composed of CD11b+ macrophages, with very few CD3+ T-lymphocytes. In contrast, T-lymphocytes are more abundant in adult GBM tissue samples. RNA sequencing of macrophages isolated from primary tumor samples revealed that DIPG- and adult GBM-associated macrophages both express gene programs related to ECM remodeling and angiogenesis, but DIPG-associated macrophages express substantially fewer inflammatory factors than their adult GBM counterparts. Examining the secretome of glioma cells, we found that patient-derived DIPG cell cultures secrete markedly fewer cytokines and chemokines than patient-derived adult GBM cultures. Concordantly, bulk and single-cell RNA sequencing data indicates low to absent expression of chemokines and cytokines in DIPG. Together, these observations suggest that the inflammatory milieu of the DIPG tumor microenvironment is fundamentally different than adult GBM. The low intrinsic inflammatory signature of DIPG cells may contribute to the lack of lymphocytes and non-inflammatory phenotype of DIPG-associated microglia/macrophages. Understanding the glioma subtype-specific inflammatory milieu may inform the design and application of immunotherapy-based treatments. Overall design: RNA-seq of primary isolated microglia/macrophages from early post-mortem DIPG tissue samples, pediatric normal cortex, and adult GBM tissue samples. Libraries were sequenced on Illumina NextSeq 500, 1x75.
Non-inflammatory tumor microenvironment of diffuse intrinsic pontine glioma.
Sex, Specimen part, Subject
View SamplesWe studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis.
Saturated fat stimulates obesity and hepatic steatosis and affects gut microbiota composition by an enhanced overflow of dietary fat to the distal intestine.
Sex, Specimen part
View Samples