The noncluster homeodomain containing gene, HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell Acute Lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgH-TLX1Tg mice, which developed mature B cell lymphoma after a long latency period suggesting the requirement of additional mutations to initiate malignancy.
Ectopic TLX1 expression accelerates malignancies in mice deficient in DNA-PK.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comprehensive analysis of microRNA (miRNA) targets in breast cancer cells.
Specimen part, Cell line
View SamplesmiRNAs regulate mRNA stability and translation through the action of the RNAi-induced silencing complex. In this study, we systematically identified endogenous miRNA target genes by using AGO2 immunoprecipitation (AGO2-IP) and microarray analyses in two breast cancer cell lines, MCF7 and MDA-MB-231, representing luminal and basal-like breast cancer, respectively. The expression levels of ~70% of the AGO2-IP mRNAs were increased by DROSHA or DICER1 knockdown. In addition, integrated analysis of miRNA expression profiles, mRNA-AGO2 interaction, and the 3'-UTR of mRNAs revealed that >60% of the AGO2-IP mRNAs were putative targets of the fifty most abundantly expressed miRNAs.
Comprehensive analysis of microRNA (miRNA) targets in breast cancer cells.
Specimen part, Cell line
View SamplesWe examined the efffects of ligating CD4 expressed by primary human peripheral blood monocytes with soluble MHC Class II.
CD4 ligation on human blood monocytes triggers macrophage differentiation and enhances HIV infection.
Specimen part, Treatment
View Samples[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice
The aryl hydrocarbon receptor mediates UVB radiation-induced skin tanning.
Sex, Specimen part
View SamplesA role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the antimicrobial mechanism is unclear. Here, we demonstrate that vitamin A mediates host defense through regulation of cellular cholesterol content. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3, the biologically active forms of vitamin A and vitamin D respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Gene expression profiling reveals that ATRA but not 1,25D3 triggers a lipid metabolism and efflux pathway, including expression of lysosomal lipid transport gene NPC2. ATRA-induced decrease in total cellular cholesterol content, subcellular lipid reorganization, lysosomal acidification and antimicrobial activity are all dependent upon expression of NPC2. Finally, the addition of HIV-protease inhibitors known to inhibit cholesterol efflux, Ritonavir and Nelfinavir, blocked both ATRA-induced cholesterol decrease as well as antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated host defense mechanism against M. tuberculosis requires regulation of cellular cholesterol.
All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2.
Specimen part, Disease, Disease stage, Treatment, Subject
View SamplesThe aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in adaptive cell functions, and highly active in the epidermis. AhR-ligands can accelerate keratinocyte differentiation, but a precise role for AhR in the skin barrier is unknown. We here show that transepidermal water loss (TEWL), a parameter of skin barrier integrity, is high in AhR-deficient (AhR-KO) mice. Experiments with conditionally AhR-deficient mouse lines identified keratinocytes as the major responsible cell population for high TEWL. Electron microscopy showed weaker inter-cellular connectivity in the epidermis of keratinocytes in AhR-KO mice, and gene expression analysis identified many barrier-associated genes as AhR targets. Moreover, AhR-deficient mice had higher inter-individual differences in their microbiome. Interestingly, removing AhR-ligands from the diet of wild-type mice mimicked AhR-deficiency regarding the impaired barrier. Vice versa, re-addition of the plant-derived ligand indole-3-carbinol (I3C) rescued the barrier deficiency even in aged mice. Our results suggest that functional AhR expression is critical for skin barrier integrity and that AhR represents a molecular target for the development of novel therapeutic approaches for skin barrier diseases, including dietary intervention.
Aryl Hydrocarbon Receptor in Keratinocytes Is Essential for Murine Skin Barrier Integrity.
Sex, Specimen part, Treatment, Time
View Sampleshuman blood monocytes were isolated, activated and harvested at several timepoints
NOD2 triggers an interleukin-32-dependent human dendritic cell program in leprosy.
Specimen part
View SamplesEffective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. Here the regulation of these key functions was investigated in human blood-derived macrophages. IL-10 induced the phagocytic pathway, including CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxLDL. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of the spectrum of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form of the disease and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity in bacterial infections.
Divergence of macrophage phagocytic and antimicrobial programs in leprosy.
Specimen part
View SamplesHomeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxd4 during cartilage development, we observed severe defects, namely physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, we performed gene expression profiling using the Affymetrix microarray platform.
Microarray Analysis of Defective Cartilage in Hoxc8- and Hoxd4-Transgenic Mice.
Specimen part
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