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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Whole genome transcriptional analysis of monocytes/macrophages purified from bone marrow of xeno-transplanted mice

ABSTRACT: The development and progression of CLL are dependent upon a complex microenvironmental network of cellular and molecular signals. As an example the in vitro survival of CLL cells is supported by nurse-like cells, which have been identified as a CLL-specific tumor-associated macrophage (TAM) population. However little is known regarding the role of TAMs in CLL development and progression. In the CLL xenograft model based on the engraftment of MEC1 human CLL cell line into Rag2-/-Î³c-/-, we analyzed the whole-genome transcriptome of TAMs isolated from the bone marrow. We found an enrichment of genes involved in inflammation and interaction between TAMs and leukemic cells. Rag2-/-Î³c-/- were injected intravenously with MEC1 cells and sacrificed at early stage of leukemia with age-matched wt Rag2-/-Î³c-/- mice (n=3/group). RNA was isolated from bone marrow murine monocytes/macrophages purified by magnetic separation and processed for illumina whole-genome gene expression direct-hybridization assay.

ORGANISM(S): Mus musculus

SUBMITTER: Michela Riba

PROVIDER: E-GEOD-57785 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Whole genome transcriptional analysis of leukemic CLL cells purified from bone marrow of xeno-transplanted mice

Project description:The development and progression of CLL are dependent upon a complex microenvironmental network of cellular and molecular signals. As an example the in vitro survival of CLL cells is supported by nurse-like cells, which have been identified as a CLL-specific tumor-associated macrophage (TAM) population. However little is known regarding the role of TAMs in CLL development and progression. In the CLL xenograft model based on the engraftment of MEC1 human CLL cell line into Rag2-/-Î³c-/-, we analyzed the whole-genome transcriptome of leukemic B cells, exposed in vivo to TAMs, isolated from the bone marrow. We found an enrichment of genes involved in inflammation and interaction between TAMs and leukemic cells. Rag2-/-Î³c-/- were injected intravenously with MEC1 cells and sacrificed at early stage of leukemia (n=3). RNA was isolated from: i) in vitro pre-injected human CD19+ MEC1 cells and ii) human CD19+ MEC1 cells purified from murine bone marrow by magnetic separation and processed for illumina whole-genome gene expression direct-hybridization assay

2016-02-16 | E-GEOD-57787 | biostudies-arrayexpress

Whole genome transcriptional analysis of monocytes/macrophages purified from bone marrow of xeno-transplanted mice

2016-02-16 | GSE57785 | GEO

Whole genome transcriptional analysis of leukemic CLL cells purified from bone marrow of xeno-transplanted mice

2016-02-16 | GSE57787 | GEO

Comparison of gene expression profile in RAG2+ B lineage cells from the small intestinal lamina propria and RAG2+ B lineage cells from the bone marrow

2013-07-12 | GSE48805 | GEO

Selective Targeting of the Proliferating Compartment in Chronic Lymhocytic Leukemia by Inhibition or Downregulation of Aurora Kinases

Project description:Chronic lymphocytic leukemia (CLL) B-cells receive signals from the lymph node and bone marrow (BM) microenvironments that regulate their survival and proliferation. These signals and the pathways that propagate them to the interior of the cell represent potential targets for therapeutic intervention. To characterize the pathways that are activated by the BM microenvironment in CLL cells in vivo, we performed gene expression profiling of tumor cells purified from BM and peripheral blood. Functional classification analysis revealed that the most frequently upregulated genes in BM-CLL cells are genes involved in cell cycle and mitosis. Among the most significantly overexpressed were the Aurora A and B kinases. To investigate whether these kinases could represent potential therapeutic targets in CLL, we performed RNA interference experiments in the CLL cell lines MEC1 and EHEB. Downregulation of Aurora A and B inhibited the proliferation and induced apoptosis in these cells. Similar effects were observed with the pan-Aurora kinase inhibitor VX-680 in primary CLL cells induced to proliferate by CpG-ODN and IL-2. VX-680 also inhibited leukemia growth in vivo in a mouse model of CLL. These data suggest that inhibition of Aurora kinases could represent a potential strategy to selectively target the proliferating compartment in CLL. To identify gene expression related to microenvironmental stimuli in B-cell Chronic Lymphocytic Leukemia (CLL) cells in vivo, expression profiles of CLL cells purified (>95%) from bone marrow (BM) and peripheral blood (PB) were compared. Paired BM and PB samples from 6 individuals were used for this analysis.

2011-07-25 | E-GEOD-30896 | biostudies-arrayexpress

Comparison of gene expression profile in RAG2+ B lineage cells from the small intestinal lamina propria and RAG2+ B lineage cells from the bone marrow

Project description:We used a RAG2-GFP reporter mouse to show that RAG+ B lineage cells can be found in the small intestinal lamina proria in normally-housed mice at weaning age. We used microarry expression analysis to compare the RAG2+ population in the gut to the RAG2+ B lineage population in the bone marrow. Microarray was used to compare RAG2+ lamina propria B cells to RAG2+ bone marrow B cells. For each experiment, RAG2-GFP+ cells from 8-12 post-natal day 17-25 RAG2-GFP reporter mice were sorted from small intestinal lamina propria lymphocyte preparations and bone marrow. RNA extracted from trizol was used for the analysis. 3 independent replicates were performed.

2013-07-12 | E-GEOD-48805 | biostudies-arrayexpress

Expression data of Rag2-deficient Ets1++ and Rag2-deficient Ets1-- mature NK cells and WT bone marrow progenitors

Project description:Expression profiling of Rag2-deficient Ets1++ and Rag2-deficient Ets1-- mature NK cells and WT bone marrow progenitors, WT T cells, and WT Pro B cells

2012-08-10 | GSE37301 | GEO

Transcriptomic analysis of femoral diaphysis and primary osteoprogenitor cells cultures from mouse strains with SHIP1 deficiency and controls

Project description:Investigation of the SHIP1 (Inpp5d)-dependent and Rag2/Il2rg-dependent transcriptional changes in bone and osteoprogenitor cells cultures from murine strains with SHIP1 deficiency (Inpp5dm1Btlr/ m1Btlr, http://www.informatics.jax.org/allele/key/65037) and controls. Specifically, transcriptomic analysis was performed from femoral diaphysis from SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+/styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype). Alternatively, osteoprogenitor cells isolated from bone marrow from the same genotypes as above were differentiated in vitro into primary osteoclasts in the presence or absence of RANKL. After 5 days, RNA was extracted from these cultures for transcriptomic analysis (n=3 for each genotype). Experimental Designs: Transcripts were analyzed in femoral diaphysis of SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype). Alternatively, transcripts were analyzed in primary osteoclast cultures from bone marrow cells isolated from SHIPstyx/styx, SHIP1+/styx, wild-type (C57BL6/J), Rag2-/-/Il2rg-/-/SHIP1styx/styx, Rag2-/-/Il2rg-/-/SHIP1+styx, and Rag2-/-/Il2rg-/-/SHIP1+/+ mice (n=3 for each genotype), which were supplemented or not with RANKL.

2024-02-21 | E-MTAB-13164 | biostudies-arrayexpress

Selective Targeting of the Proliferating Compartment in Chronic Lymhocytic Leukemia by Inhibition or Downregulation of Aurora Kinases

2011-07-26 | GSE30896 | GEO

High throughput sequencing of immunoglobulin (Ig) heavy (IgH) and light (IgL) chain repertoires

Project description:We used 454 sequencing to assess the repertoire of B cell subsets from bone marrow, spleen, and small intestinal lamina propria from two mouse strains. We used a RAG2-GFP reporter mouse strain (129Sve background) to isolate CD19+ RAG2+ B lineage cells from bone marrow and small intestinal lamina propria and total splenic B cells. We used 5' RACE to amplify cDNA libraries using primers specific for the mu constant region of IgH and the Ig kappa constant region. We also used this technique to analyze total B cell libraries from Swiss Webster germ-free mice to compare to littermate controls that were cohoused with regular specific pathogen free (SPF) mice for 7 days. Examination of the Ig kappa repertoire and IgH repertoire in RAG2+ bone marrow B lineage cells compared to RAG2+ small intestinal lamina propria B lineage cells or total splenic B cells. There are 8 (Ig kappa) or 4 (IgH) independent experiments comparing repertoires in RAG2-GFP mice. Each experiment in RAG2-GFP+ mice consisted of a pool of 8-12 mice. There are 3 experiments comparing germ-free to colonized mouse total B cell repertoires, each consisting of one mouse per condition.

2013-07-16 | E-GEOD-48870 | biostudies-arrayexpress

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