Project description:Matrices of TPM-normalized counts from RNAseq data for the three phase II clinical trials (IMvigor210, POPLAR, IMmotion150) and the phase I clinical trial PCD4989g.
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.
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.
Project description:In BRE-GFP transgenic mice BMP activated cells are marked by GFP expression. Analysis of GFP+ and GFP- LSK-SLAM HSC enriched fractions from fetal liver and adult bone marrow shows the interinsic differences in the genetic program of these two HSC enriched fractions. RNAseq of GFP+ and GFP- LSK-SLAM cells from BRE-GFP transgenic mice Fetal liver and adult bone marrow