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9c1776ab-2ed8-4970-8fa4-95980414dfdf - samples

ABSTRACT: TPM matrices of counts from RNA sequencing (RNAseq) from baseline CD138+ enriched BM fractions.

PROVIDER: EGAD00001011148 | EGA |

REPOSITORIES: EGA

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c6a3480a-34b1-4b1d-bfff-0c323a97217d - samples

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Interferon activation in bone marrow long-lived plasma cells in systemic lupus erythematosus

Project description:While durable antibody responses from long-lived plasma cell (LLPC) populations are important for protection against pathogens, LLPC may be harmful if they produce antibodies against self-proteins or self-nuclear antigens as occurs in autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the elimination of autoreactive LLPC may improve the treatment of antibody-driven autoimmune diseases. However, LLPC remain a challenging therapeutic target. Here, we compare the matched bone marrow and blood plasma cell compartments of SLE and healthy donors (HD). We show a similar distribution of CD138- and CD138+ plasma cells (PC), including putative LLPC (CD19- CD138+ CD38+), between SLE and HD bone marrow (BM). For both SLE and HD, CD138+ PC are at a higher frequency in BM than peripheral blood (PBL). Expression of Ki-67 associates with the PBL compartment where it is found on all PC subsets regardless of CD19 or CD138 expression. Transcriptomic analysis identifies an interferon gene signature in transitional B cells in the SLE BM, but surprisingly also in the BM PC derived from SLE. PC phosphorylate STAT1 in response to type I IFN stimulation in vitro. Circulating PC bind type I IFN receptor-blocking antibody anifrolumab, though to a lesser degree than circulating B cells. Anti-nuclear autoantibodies are found in the BM supernatant and PBL serum of SLE patients. SLE BM-derived PC have increased survival compared to their PBL counterparts when treated with selinexor. In summary, these findings show evidence of IFN activation in BM PC from SLE.

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Human native bone marrow CD200 positive mesenchymal stromal cells exhibit characteristics of cells forming the hematopoietic stem cell niche

Project description:Bone marrow (BM) mesenchymal stem/stromal cells are non-hematopoietic (CD45-), non-endothelial (CD31-) multipotential cells capable to differentiate into osteoblastes, chondrocytes and adipocytes. In addition, different subpopulations of MSCs and some of their derivatives (early osteoblastic lineage cells) were shown to form HSC-niche. This makes a complex picture of the relationship between MSCs and HSCs. Despite growing data in mice model, few describe the human counterpart. The BM CD200+ and CD271+ fractions were previously shown to be enriched in native MSCs in human. Herein, we found heterogeneity in expression of CD200 within CD45-/CD31-/CD271+ human BM fraction. We thus selected CD200+ and CD200- cells from CD45-/CD31-/CD271+ BM samples and we analyzed their transcriptome. The differential display of gene expression between these two types of BM fractions will give new insights in the identification of native human MSCs.

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Human Organotypic Smoke Street

Project description:The aim of this study was to develop human bronchial and nasal epithelium culture models that are relevant to investigate the impact of cigarette smoke (CS) observed in vivo in respiratory tract tissues in contact with inhaled CS. We used two organotypic cultures generated from primary cells derived from non-smoking donors that contain fibroblasts and epithelial cells in order to reproduce as closely as possible the in vivo situation. To mimic the smoking behavior of a moderate smoker during one day, human tissue cultures (bronchial and nasal epithelium) were exposed repeatedly and directly at the air/liquid interface (using the Vitrocell(R) System) to two doses (high 4.2 ug TPM/cm2 and low 2.2 ug TPM/cm2 per cigarette) of the whole smoke generated by one cigarette or to humidified air (sham). CS exposure was repeated four times with one hour intervals between each cigarette. Various endpoints (e.g., gene and microRNA expression, CYP activity, pro-inflammatory markers release, differential cell counts, cytotoxicity measurement) were then captured to assess the baseline (time 0) and early responses of the tissues after exposure (4 hours) as well as the recovery phase (24 and 48 hours).

2013-12-11 | E-MTAB-1721 | biostudies-arrayexpress

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