The immune system plays a pivotal role in susceptibility to and progression of a variety of diseases. Due to its strong genetic basis, heritable differences in immune function may contribute to differential disease susceptibility between individuals. Genetic reference populations, such as the BXD (C57BL/6J X DBA/2J) panel of recombinant inbred (RI) mouse strains, provide a unique model through which to integrate baseline phenotypes in healthy individuals with heritable risk for disease because of the ability to combine data collected from these populations across multiple studies and time. We performed basic immunophenotyping (e.g. percentage of circulating B and T lymphocytes and CD4+ and CD8+ T cell subpopulations) in peripheral blood of healthy mice from 41 BXD RI strains to define the phenotypic variation in this model system and to characterize the genetic architecture that unlerlies these traits. Significant QTL models that explained the majority (50-77%) of phenotypic variance were derived for each trait and for the T:B cell and CD4+:CD8+ ratios. Combining QTL mapping with spleen gene expression data uncovered two quantitative trait transcripts (QTTs), Ptprk and Acp1, that which are candidates for heritable differences in the relative abundance of helper and cytotoxic T cells. These data will be valuable in extracting genetic correlates of the immune system in the BXD panel. In addition, they will be a useful resource in prospective, phenotype-driven model selection to test hypotheses about differential disease or environmental susceptibility between individuals with baseline differences in the composition of the immune system.
Identifying genetic loci and spleen gene coexpression networks underlying immunophenotypes in BXD recombinant inbred mice.
Sex, Specimen part
View SamplesA robust set of CNS transcript changes was defined by comparing microarray data that describe the injury response of the rat retina [Vazquez-Chona et al., IOVS 2004; GSE1001], brain [Matzilevich et al., J Neurosci Res 2002; GSE1911], and spinal cord [Di Giovanni et al., Ann Neurol 2003; GDS63]. We determined the CNS injury genes that were expressed in cultured astrocytes from rat cortex [GSM34300] and from human optic nerve head [Yang et al., Physiol Genomics 2004; GDS532].
Genetic networks controlling retinal injury.
No sample metadata fields
View SamplesTwo critical events that are required for normal transition from fetal to extrauterine life are development of the alveoli that allow for efficient gas exchange in the lung and relaxation of the pulmonary vascular smooth muscle. Patients with congenital diaphragmatic hernia (CDH) have abnormal lung and pulmonary vascular development that results in a lethal combination of lung hypoplasia and pulmonary hypertension. To better understand the mechanisms responsible for abnormal lung and pulmonary vascular development and function we generated Pbx1/2 conditional knockout mice that lack Pbx1 and Pbx2 expression in the lung mesenchyme. Pbx1 has previously been shown to be required for normal diaphragm development, however its role in alveologenesis, and the mechanisms responsible for pulmonary hypertension, has not been studied. We found that Pbx1/2 CKO mice have failure of alveologenesis and die of severe pulmonary hypertension by 2 to 3 weeks of age. In order to better understand the downstream genetic mis-regulation caused by deletion of Pbx1/2, and identify their potential transcriptional targets, we carried out transcriptional profiling of Pbx1/2 CKO and control mice starting at postnatal day 3 (P3), when a histological phenotype first becomes apparent, and then working back to the time of birth (P0), and embryonic day 14 (E14) when the pulmonary vascular smooth muscle is developing.
PBX transcription factors drive pulmonary vascular adaptation to birth.
Specimen part
View SamplesWe have combined large-scale mRNA expression and gene mapping methods to identify genes and loci that control hematopoietic stem cell (HSC) functioning. mRNA expression levels were measured in purified HSC isolated from a panel of densely genotyped recombinant inbred mouse strains. Quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts were mapped. Comparison of the physical transcript position with the location of the controlling QTL identified polymorphic cis-acting stem cell genes. In addition, multiple trans-acting control loci were highlighted that modify expression of large numbers of genes. These groups of co-regulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of strong candidate genes involved with HSC turnover. We compared expression QTLs in HSC and brain from the same animals, and document both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of co-regulated transcripts.
Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Treatment
View SamplesChronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia. Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality. Overall design: High temporal analysis of global gene expression in the DRG following spared nerve injury (SNI) correlated with behavior taken at the same time points. Expression and behavioral sensitivity taken at least daily over the first 10 days post SNI.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Cell line, Subject
View SamplesChronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia (DRG). Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related, whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas, depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality.
Mechanistic Differences in Neuropathic Pain Modalities Revealed by Correlating Behavior with Global Expression Profiling.
Sex, Specimen part, Treatment
View SamplesMacrophages in tumor microenvironment have been characterized as M1- and M2-polarized subtypes. This study sought to investigate the effects of different macrophage subtypes on the biological behavior and global gene expression profiles of lung cancer cells. Expression microarray and bioinformatics analyses indicated that the different macrophage subtypes mainly regulated genes involved in cell cycle, cytoskeletal remodeling, coagulation, cell adhesion and apoptosis pathways in A549 cells, a pattern that correlated with the altered behavior of A549 cells observed after coculture with macrophage subtypes.
Opposite Effects of M1 and M2 Macrophage Subtypes on Lung Cancer Progression.
Specimen part, Cell line
View SamplesIn order to identify patterns of gene expression associated with biological effects in THP-1 cells induced by F3, we performed a transcriptomic analysis on the THP-1 control and F3-treated THP-1 cells by oligonucleotide microarray
Ganoderma lucidum polysaccharides in human monocytic leukemia cells: from gene expression to network construction.
Cell line
View SamplesThe CLS1/CAF co-culture maintained the cancer stemness. This cancer stemness was lost when the CAF feeder cells were removed during passaging.
Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling.
Cell line
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