Investigation of immune-cell differentiation and function is limited by shortcomings of suitable and scalable experimental systems. Here we show that retroviral delivery of an estrogen-regulated form of Hoxb8 into mouse bone marrow cells can be used along with Flt3 ligand to conditionally immortalize early hematopoietic progenitor cells (Hoxb8-FL cells). Hoxb8-FL cells have lost self-renewal capacity and potential to differentiate into megakaryocytes and erythrocytes but retain the potential to differentiate into myeloid and lymphoid cells. They differentiate in vitro and in vivo into macrophages, granulocytes, dendritic cells, B lymphocytes and T lymphocytes that are phenotypically and functionally indistinguishable from their primary counterparts. Quantitative in vitro assays indicate that myeloid and B-cell potential of Hoxb8-FL cells is comparable to that of primary lymphoid-primed multipotent progenitors, whereas T-cell potential is diminished. The simplicity of this system and the unlimited proliferative capacity of Hoxb8-FL cells will enable studies of immune-cell differentiation and function.
Hematopoietic progenitor cell lines with myeloid and lymphoid potential.
Specimen part
View SamplesMethylene diphenyl diisocyanate is a chemical known to cause asthma. The present study uses mice to investigate exposure-induced changes in lung gene expression and effects of a chloride channel inhibitor
Analysis of Lung Gene Expression Reveals a Role for Cl<sup>-</sup> Channels in Diisocyanate-induced Airway Eosinophilia in a Mouse Model of Asthma Pathology.
Sex
View SamplesWe hypothesized that gene expression in lungs of Fra-1+/+ and Fra-1-/- mice are divergent thus contributing fibrosis. More specifically, Fra-1-/- mice are increased susceptible to fibrosis. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Fra-1+/+ and Fra-1-/- mice at early time point.
Expression profiling of genes regulated by Fra-1/AP-1 transcription factor during bleomycin-induced pulmonary fibrosis.
Sex, Age, Specimen part
View SamplesRATIONALE: Mechanical ventilation (MV) is an indispensable therapy for critically ill patients with acute lung injury and the adult respiratory distress syndrome. However, the mechanisms by which conventional MV induces lung injury remain unclear. OBJECTIVES: We hypothesized that disruption of the gene encoding Nrf2, a transcription factor which regulates the induction of several antioxidant enzymes, enhances susceptibility to ventilator-induced lung injury (VILI), while antioxidant supplementation attenuates such effect. METHODS: To test our hypothesis and to examine the relevance of oxidative stress in VILI, here we have assessed lung injury and inflammatory responses in Nrf2-deficient (Nrf2(-/-)) mice and wildtype (Nrf2(+/+)) animals following acute (2 h) injurious model of MV with or without administration of antioxidant. MEASUREMENTS AND MAIN RESULTS: Nrf2(-/-) mice displayed greater levels of lung alveolar and vascular permeability and inflammatory responses to MV as compared to Nrf2(+/+) mice. Nrf2-deficieny enhances the levels of several pro-inflammatory cytokines implicated in the pathogenesis of VILI. We found diminished levels of critical antioxidant enzymes and redox imbalance by MV in the lungs of Nrf2(-/-) mice; however antioxidant supplementation to Nrf2(-/-) mice remarkably attenuated VILI. When subjected to clinically relevant prolong period of MV, Nrf2(-/-) mice displayed greater levels of VILI than Nrf2(+/+) mice. Expression profiling revealed lack of induction of several VILI genes, stress response and solute carrier proteins and phosphatases in Nrf2(-/-) mice. CONCLUSIONS: Collectively, our data demonstrate for the first time a critical role for Nrf2 in VILI, which confers protection against cellular responses induced by MV by modulating oxidative stress.
Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice.
No sample metadata fields
View SamplesBackground: In multiple sclerosis (MS), immune up-regulation is coupled to subnormal immune response to interferon-β (IFN-β) and low serum IFN-β levels. The relationship between the defect in IFN signalling and acute and long-term effects of IFN-β on gene expression in MS is inadequately understood. Methods: We profiled IFN-β-induced transcriptome shifts, using high-resolution microarrays on 227 mononuclear cell samples from IFN-β-treated MS Complete Responders (CR) stable for five years, and stable and active Partial Responders (PR), stable and active untreated MS, and healthy controls. Findings: IFN-β injection induced short-term changes in 1,200 genes compared to baseline expression after 4-day IFN washout. Pre-injection after washout, and in response to IFN-β injections, PR more frequently had abnormal gene expression than CR. Surprisingly, short-term IFN-β induced little shift in Th1/Th17/Th2 gene expression, but up-regulated immune-inhibitory genes (ILT, IDO1, PD-L1). Expression of 8,800 genes was dysregulated n therapy-naïve compared to IFN-β-treated patients. These long-term changes in protein-coding and long non-coding RNAs affect immunity, synaptic transmission, and CNS cell survival, and correct the disordered therapy-naïve transcriptome to near-normal. In keeping with its impact on clinical course and brain repair in MS, long-term IFN-β treatment reversed the overexpression of proinflammatory and MMP genes, while enhancing genes involved in the oligodendroglia-protective integrated stress response, neuroprotection, and immunoregulation. In the rectified long-term signature, 277 transcripts differed between stable PR and CR patients.
Interferon-β corrects massive gene dysregulation in multiple sclerosis: Short-term and long-term effects on immune regulation and neuroprotection.
Age, Specimen part
View SamplesWe hypothesize that gene expression in the Type II cells of Nrf2+/+ and Nrf2-/- mice are divergent thus contributing the cell growth. More specifically, type II cells from Nrf2-/- mice have increased reactive oxygen species that cause the impaired cell growth. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences between Nrf2+/+ and Nrf2-/- cells.
Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection.
No sample metadata fields
View SamplesAnalysis of genes regulated by STC1 down-regulation in mouse 4T1 derived clone, 4T1ch9. STC1 expression is associated with tumor growth and metastasis. This study looks at genes affected when STC1 expression is down-regulated by STC1 shRNA.
STC1 expression is associated with tumor growth and metastasis in breast cancer.
Cell line
View SamplesWistar rats, purchased from BRL (Fullinsdorf/BL, Switzerland), and WBN/Kob rats, purchased from SLC Inc. (Shizuoka, Japan), were specific pathogen-free. Rats were housed in groups of maximally 4 instandard cages (1,820 cm2 bottom area) and kept in our animal facility for various time periods between 1 week and 36 weeks (free access to standard rat chow and water; specific pathogen-free conditions; 20 degree C; day/night cycle simulated by artificial lighting of 50 lx from 7 a.m. to 7 p.m., dimmed in the remaining hours to almost complete darkness; air humidity 50 to 60%). Prior to surgery or sacrifice, the rats were fasted overnight (16 to18 h) with free access to water. All manipulations conformed with the Swiss Federal Guidelines on Animal Experiments and were approved by the local ethics committee.
Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis.
Sex, Age, Specimen part, Time
View SamplesRight ventricular samples were serially acquired during surgical repair of ventricular septal defect. Expression profiling revealed three patterns of gene expression: (1) increased expression above control levels within one hour of cardioplegic arrest, with further amplification during early reperfusion; (2) increased expression limited to the reperfusion phase; and (3) reduced expression during reperfusion.
Early gene expression profiles during intraoperative myocardial ischemia-reperfusion in cardiac surgery.
No sample metadata fields
View SamplesInterstitial cells of Cajal (ICC) have important functions in regulation of motor activity in the gastrointestinal tract. In murine small intestine ICC are gathered in the region of the myenteric plexus (ICC-MY) and within the deep-muscular plexus near the submucosal surface of the circular muscle layer (ICC-DMP). These two classes of ICC have different physiological functions.
Differential gene expression in functional classes of interstitial cells of Cajal in murine small intestine.
No sample metadata fields
View Samples