gene expression profiles of leukocytes from blood (WBCs) and spleen harvested at an early (two hours) time point after injury or sham injury in mice subjected to trauma-hemorrhage, burn injury or lipopolysaccharide (LPS)-infusion at three experimental sites
Commonality and differences in leukocyte gene expression patterns among three models of inflammation and injury.
No sample metadata fields
View SamplesTo explore global molecular changes in smooth muscle in response to PDGFR activation, primary human bladder smooth muscle cells were treated with 1 nM PDGF-BB (hereafter PDGF) for 0, 4 or 24 h. Total RNA were prepared, and analyzed using expression profiling, and subjected to bioinformatic and functional interrogation.
Integration of proteomic and transcriptomic profiles identifies a novel PDGF-MYC network in human smooth muscle cells.
Specimen part
View SamplesMale Wistar rats weighing 90-120 g were acclimatized for one week and fed standard laboratory chow, at which time the animals were divided into two groups. Animals were then pair-fed for 8 weeks a regular laboratory chow and water ad libitum or Lieber-DeCarli diet (36% calories from ethanol). Control animals received the iso-caloric amount of dextrose to replace ethanol. After 8 weeks of differential feeding rats were euthanized, the pancreas immediately dissected and stored at -80?C until RNA isolation. RNA expression was analyzed using Affymetrix RAE230A gene chips
Long-term ethanol consumption alters pancreatic gene expression in rats: a possible connection to pancreatic injury.
No sample metadata fields
View SamplesGlobal mRNA expression was compared between stable and progressive IPF using bronchoalveolar lavage derived mesenchymal stromal cells
Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with Idiopathic Pulmonary Fibrosis.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia.
Age, Specimen part, Disease, Disease stage
View SamplesWe demonstrate a promising approach to identify robust molecular markers for targeted treatment of acute myeloid leukemia. We show that our method outperforms several state-of-the-art approaches in identifying molecular markers replicated in validation data and predicting drug sensitivity accurately.
A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia.
Age, Specimen part, Disease, Disease stage
View SamplesWe demonstrate a promising approach to identify robust molecular markers for targeted treatment of acute myeloid leukemia. We show that our method outperforms several state-of-the-art approaches in identifying molecular markers replicated in validation data and predicting drug sensitivity accurately. Finally, we identify SMARCA4 as a marker and driver of sensitivity to topoisomerase II inhibitors, mitoxantrone and etoposide, in AML by showing that cell lines transduced to have high SMARCA4 expression reveal dramatically increased sensitivity to these agents. Overall design: We measured the gene expression of samples from 30 different AML patients with acute myeloid leukemia in order to identify reliable gene expression markers for drug sensitivity. We used this dataset for validation. This Series represents 12 patient samples.
A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia.
Age, Specimen part, Disease, Disease stage, Subject
View SamplesBackground: Activation of microglia, the resident immune cells of the central nervous system, is a prominent pathological hallmark of Alzheimer's disease (AD). However, the gene expression changes underlying microglia activation in response to tau pathology remain elusive. Furthermore, it is not clear how murine gene expression changes relate to human gene expression networks. Methods: Microglia cells were isolated from rTg4510 tau transgenic mice and gene expression was profiled using RNA sequencing. Four age groups of mice (2-, 4-, 6-, and 8-months) were analyzed to capture longitudinal gene expression changes that correspond to varying levels of pathology, from minimal tau accumulation to massive neuronal loss. Statistical and system biology approaches were used to analyze the genes and pathways that underlie microglia activation. Differentially expressed genes were compared to human brain co-expression networks. Results:Statistical analysis of RNAseq data indicated that more than 4000 genes were differentially expressed in rTg4510 microglia compared to wild type microglia, with the majority of gene expression changes occurring between 2- and 4-months of age. These genes belong to four major clusters based on their temporal expression pattern. Genes involved in innate immunity were continuously up-regulated, whereas genes involved in the glutamatergic synapse were down-regulated. Up-regulated innate inflammatory pathways included NF-?B signaling, cytokine-cytokine receptor interaction, lysosome, oxidative phosphorylation, and phagosome. NF-?B and cytokine signaling were among the earliest pathways activated, likely driven by the RELA, STAT1 and STAT6 transcription factors. The expression of many AD associated genes such as APOE and TREM2 was also altered in rTg4510 microglia cells. Differentially expressed genes in rTg4510 microglia were enriched in human neurodegenerative disease associated pathways, including Alzheimer's, Parkinson's, and Huntington's diseases, and highly overlapped with the microglia and endothelial modules of human brain transcriptional co-expression networks. Conclusion: This study revealed temporal transcriptome alterations in microglia cells in response to pathological tau perturbation and provides insights into the molecular changes underlying microglia activation during tau mediated neurodegeneration. Overall design: Compare the microglial cell gene expression changes in rTg4510 tau transgenic mice and wild type at four age groups (2-, 4-, 6-, and 8-months) The rTg4510 mouse is a tauopathy model providing researchers with temporal control over mutant tau transgene expression. The mice express a repressible form of human tau containing the P301L mutation that has been linked with familial frontotemporal dementia. More information can be found here, https://www.alzforum.org/research-models/rtgtaup301l4510
Genome-wide RNAseq study of the molecular mechanisms underlying microglia activation in response to pathological tau perturbation in the rTg4510 tau transgenic animal model.
Sex, Age, Specimen part, Cell line, Subject
View SamplesYY1 is a ubiquitously expressed transcription factor that has been demonstrated to be essential for pro-B cell development. However, the role of YY1 in other B cell populations has never been investigated. It has been proposed that YY1 is a key regulator for the germinal center B cell program since the YY1 motif was present in much higher frequency in germinal center B cell signature genes than signature genes of other B cell subsets. Indeed, in accord with this prediction, we demonstrated that deletion of YY1 by Cg1-Cre completely prevented differentiation of naïve B cells into germinal center B cells and plasma cells after antigen stimulation. To determine if YY1 was also required for the differentiation of other B cell populations, we deleted YY1 with CD19-Cre and found that all peripheral B cell subsets including B1 B cells require YY1 for their differentiation. By deleting YY1 acutely with ER-Cre, we demonstrated that all B cell subsets require YY1 for their maintenance. ChIP-seq shows that YY1 predominantly binds to promoters, and pathway analysis of the genes which bind YY1 show that they are enriched in ribosomal functions, mitochondrial functions such as bioenergetics, and functions related to transcription, such as mRNA splicing, metabolism of RNA. By RNA-seq analysis of differentially expressed genes, we demonstrated that YY1 normally activates genes involved in mitochondrial bioenergetics, while it normally downregulates genes involved in transcription, mRNA splicing, NF-kB signaling pathways, AP-1 transcription factor network, chromatin remodeling, cytokine signaling pathways, cell adhesion, cell proliferation and c-Myc targets. Overall design: Total RNA was prepared from RAG-/-pro-B cells, RAG-/-YY1f/f x mb1-Cre pro-B cells, RAG-/- µ+ pre-B cells, C57BL/6 follicular B cells, and C57BL/6 GC B cells. RNA was extracted using TRIzol (Life Technologies) and genomic DNA was eliminated using the genomic DNA wipeout buffer in the QuantiTect Reverse transcription kit (Qiagen). A final purification of the RNA was performed with the RNeasy kit (Qiagen). Ribosomal RNA was eliminated using Ribo-Zero Magnetic Gold Kit (Illumina).RNA samples were submitted to the Next Generation Sequencing Core, where they were processed with the NEBNext Ultra Directional RNA Library Prep Kit for Illumina and sequenced on the Illumina HiSeq. Three independent RNA-seq samples were used for RAG-/- pro-B and RAG-/- YY1f/f x mb1-Cre pro-B cells, and two samples for the other cell types.
YY1 plays an essential role at all stages of B-cell differentiation.
Sex, Specimen part, Cell line, Subject
View SamplesWe tested the effects of the antioxidant NAC (N-Acetyl-Cysteine) on gene expression in Nkx3.1-deficient mouse prostate.
Antioxidant treatment promotes prostate epithelial proliferation in Nkx3.1 mutant mice.
Age, Specimen part
View Samples