Microarray based mRNA profiling was used to identify the mechanism of action for the small molecule b-AP15.
Inhibition of proteasome deubiquitinating activity as a new cancer therapy.
Cell line, Treatment
View SamplesThe human bone marrow (BM) gives rise to all distinct blood cell lineages, including CD1c+ and CD141+ myeloid dendritic cells (DC) and monocytes. These cell subsets are also present in peripheral blood (PB) and lymphoid tissues. However, the difference between the BM and PB compartment in terms of differentiation state and immunological role of DC is not yet known. The BM may represent both a site for development as well as a possible effector site and so far, little is known in this light with respect to different DC subsets. Using genome-wide transcriptional profiling we found clear differences between the BM and PB compartment and a location-dependent clustering for CD1c+ and CD141+ was demonstrated. DC subsets from BM clustered together and separate from the corresponding subsets from PB, which similarly formed a cluster. In BM, a common proliferating and immature differentiating state was observed for the two DC subsets, whereas DC from the PB showed a more immune-activated mature profile. In contrast, BM-derived slan+ non-classical monocytes were closely related to their PB counterparts and not to DC subsets, implying a homogenous prolife irrespective of anatomical localization. Additional functional tests confirmed these transcriptional findings. DC-like functions were prominently exhibited by PB DC. They surpassed BM DC in maturation capacity, cytokine production and induction of CD4+ and CD8+ T cell proliferation. This first study on myeloid DC in healthy human BM offers new information on steady-state DC biology and could potentially serve as a starting point for further research on these immune cells in healthy conditions as well as in diseases.
Human Bone Marrow-Derived Myeloid Dendritic Cells Show an Immature Transcriptional and Functional Profile Compared to Their Peripheral Blood Counterparts and Separate from Slan+ Non-Classical Monocytes.
Specimen part
View SamplesAbstract: Human 6-sulfo LacNac (slan)+ cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DC. To gain deeper insight into the functional specialization of slan+ cells, we have compared them with both conventional myeloid DC subsets (CD1c+ and CD141+) in human peripheral blood. Using genome-wide transcriptional profiling as well as extensive functional tests, we clearly show that slan+ cells form a distinct, non-DC-like, population. They cluster away from both DC subsets and their gene expression profile evidently suggests involvement in distinct inflammatory processes. An extensive comparison with existing genomic data sets also strongly confirmed the relationship of slan+ with the monocytic compartment rather than with DC. From a functional perspective, their ability to induce CD4+ and CD8+ T cell proliferation is relatively low. Combined with the finding that antigen presentation by MHC class II is at the top of under-represented pathways in slan+ cells, this points to a minimal role in directing adaptive T cell immunity. Rather, the higher expression of complement receptors on their cell surface, together with their high secretion of IL-1 and IL-6, imply a specific role in innate inflammatory processes, which is consistent with their recent identification as non-classical monocytes. This study extends our knowledge on DC/monocyte subset biology under steady state conditions and contributes to our understanding of their role in immune-mediated diseases and their potential use in immunotherapeutic strategies.
Transcriptional profiling reveals functional dichotomy between human slan<sup>+</sup> non-classical monocytes and myeloid dendritic cells.
Specimen part
View SamplesCD14+ human monocytes differentiating into DCs in the presence of IL4 and GM-CSF were treated with agonists for RXR and its partners or vehicle 18 hours after plating (experiment with RXR and permissive partners, donor 1-3) or 14 hours after plating (experiment with nonpermissive partners, donor 4-6). Cells were harvested 12 hours thereafter. Experiments were performed in biological triplicates representing samples from three different donors.
Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.
Specimen part, Subject
View SamplesIn this study transcriptome profiling of dendritic cell subtypes was performed using various human dendritic cells.
Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.
Specimen part
View SamplesWe have replaced the right arm of chromosome IX in Saccharomyces cerevisiae with a synthetic version to generate synIXR haploids. The synthetic chromosome features multiple sequeunce modifications.
Synthetic chromosome arms function in yeast and generate phenotypic diversity by design.
Specimen part
View SamplesHere we describe microRNA profiling of a single differentiation pathway from the stem cell through to terminally differentated mature cells. Overall design: Populations corresponding to distinct stages in T lymphocyte development, from the hematopoietic stem cell-enriched Lin-Sca+Kit+ population through to mature CD4+ and CD8+ T cells were FACS-sorted to purity from the bone marrow and thymus of C57BL/6 mice. Total RNA was extract from each population from which microRNA sequencing libraries were constructed.
Dynamic microRNA gene transcription and processing during T cell development.
Specimen part, Cell line, Subject
View SamplesHere we show the microRNA genes can been very large and displaying many summarizing structural characteristics Overall design: MicroRNA biogenesis was ablated in CD4+ and CD8+ by deleted Rnasen gene (encoding Drosha). Poly A RNAs were extracted and analyzed by ultra high throughput sequencing
Dynamic microRNA gene transcription and processing during T cell development.
Specimen part, Cell line, Subject
View SamplesWe performed microarray analysis to investigate the gene expression profile changes induced by Hmg20b knock down in I/11 cells.
The DNA binding factor Hmg20b is a repressor of erythroid differentiation.
Specimen part
View SamplesThe feasibility of longitudinal metastatic biopsies for gene expression profiling in breast cancer is unexplored. Dynamic changes in gene expression can potentially predict efficacy of targeted cancer drugs.
Gene expression profiling of sequential metastatic biopsies for biomarker discovery in breast cancer.
No sample metadata fields
View Samples