Project description:The cell lineage origin of interferon-producing killer dendritic cells (IKDC), which exhibit prominent anti-tumoral activity, has been subject to debate. Although IKDC were first described as a cell type exhibiting both pDC and NK cell properties, the current view reflects that IKDC merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relationship of B220+ NK cells with regards to other NK cell subsets. We surprisingly find that, upon adoptive transfer, B220- NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells in vivo. Moreover, we unequivocally demonstrate that B220+ NK cells are highly proliferative and differentiate into mature NK cells upon in vivo adoptive transfer. Additional phenotypic, functional and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. By analogy to pre-B cells and pre-DC, we propose that B220+ NK cells should be renamed pre-NK cells. The characterization of these novel attributes to pre-NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies. Total RNA from B220+ NK cells compared to total RNA from CD27- and CD27+ NK cell subsets all isolated ex vivo from the spleen of B6.Rag-/-. Triplicatas were analysed.
Project description:Previous reports have defined three subsets of mouse NK cells on the basis of the expression of CD27 and CD11b. The developmental relationship between these subsets was unclear. To address this issue, we evaluated the overall proximity between mouse NK cell subsets defined by CD27 and CD11b expression using pangenomic gene expression profiling. The results suggest that CD27+CD11b-, CD27+CD11b+ and CD27-CD11b+ correspond to three different intermediates stages of NK cell development. Experiment Overall Design: Spleen cells from RAG-/- mice have been isolated and stained with anti-NK1.1, anti CD27 and anti CD11b antibodies. NK1.1+ cells were sorted into CD27+ CD11b-, CD27+ CD11b+ and CD27- CD11b+ subsets by flow cytometry. There are two independent replicates for each sample. Total RNA was extracted with the RNeasy microkit (Qiagen) and gene expression profiles were performed according to manufacturer instructions (Affymetrix mouse 430 2.0).
Project description:Previous reports have defined three subsets of mouse NK cells on the basis of the expression of CD27 and CD11b. The developmental relationship between these subsets was unclear. To address this issue, we evaluated the overall proximity between mouse NK cell subsets defined by CD27 and CD11b expression using pangenomic gene expression profiling. The results suggest that CD27+CD11b-, CD27+CD11b+ and CD27-CD11b+ correspond to three different intermediates stages of NK cell development.
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
Project description:The cell lineage origin of interferon-producing killer dendritic cells (IKDC), which exhibit prominent anti-tumoral activity, has been subject to debate. Although IKDC were first described as a cell type exhibiting both pDC and NK cell properties, the current view reflects that IKDC merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relationship of B220+ NK cells with regards to other NK cell subsets. We surprisingly find that, upon adoptive transfer, B220- NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells in vivo. Moreover, we unequivocally demonstrate that B220+ NK cells are highly proliferative and differentiate into mature NK cells upon in vivo adoptive transfer. Additional phenotypic, functional and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. By analogy to pre-B cells and pre-DC, we propose that B220+ NK cells should be renamed pre-NK cells. The characterization of these novel attributes to pre-NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.
Project description:In this study, we aim to establish the means to characterize cynomolgus macaque natural killer (NK) cells, and to investigate the CD27/CD11b NK maturation model in Macaca fascicularis NK cell subpopulations. The NK development studies performed mainly in mice models have demonstrated four functionally distinct subsets as defined by CD27 and CD11b, however this has not yet been established in nonhuman primates. The expression data of these macaque NK subsets will be associated with the antibody-dependent cellular cytotoxicity and missing-self responses produce by each subset.
Project description:Comparison of gene expression profiles from Mus musculus brain at age 30 months. The RNA-seq data comprise 1 groups. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:Comparison of gene expression profiles from Mus musculus brain (hemisphere) of animals kept in standard environment and enriched environment. The RNA-seq data comprise 4 groups: 2 age groups, each w/ and w/o enriched environment. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)