Project description:The aim of the study was to get insights into transcriptional alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients We compared the global gene expression profile from AML BM-MSC (n=19) to healthy donor (HD) controls (HD BM-MSC n=4)
Project description:Human bone marrow mesenchymal stromal cells (BM-MSC) could be committed toward a functional lymphoid-like stroma by a combination of TNFalpha (TNF) and Lymphotoxin alpha1/beta2 (LT) (Amé-Thomas et al Blood 2007). Bone marrow and lymph node stromal cells support FL malignant cell recruitment and growth in particular after comittment to a lymphoid-like differentiation in vitro. In addition, more than 70% of FL patients exhibit a bone marrow involvment at diagnosis. We delineate using Affymetrix U133+2.0 microarrays the gene expression profile of BM-MSC obtained from FL patients (FL-MSC) and age-matched healthy donors (HD-MSC) in order to identify a specific FL-MSC signature. In addition, we used Affymetrix microarrays to define the gene expression signature of lymphoid-like stromal cells obtained from HD-MSC by treatment with TNF/LT in vitro. This TNF/LT signature was then used to interpret the gene expression profile of FL-MSC.
Project description:The aim of the study was to get insights into transcriptional alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients We compared the global gene expression profile from AML BM-MSC (n=19) to healthy donor (HD) controls (HD BM-MSC n=4) AML BM-MSC and HD BM-MSC were isolated from bone marrow aspirates (see below) and hybridized on an Affymetrix HG-U133 Plus 2.0 GeneChip
Project description:Human bone marrow mesenchymal stromal cells (BM-MSC) could be committed toward a functional lymphoid-like stroma by a combination of TNFalpha (TNF) and Lymphotoxin alpha1/beta2 (LT) (Amé-Thomas et al Blood 2007). Bone marrow and lymph node stromal cells support FL malignant cell recruitment and growth in particular after comittment to a lymphoid-like differentiation in vitro. In addition, more than 70% of FL patients exhibit a bone marrow involvment at diagnosis. We delineate using Affymetrix U133+2.0 microarrays the gene expression profile of BM-MSC obtained from FL patients (FL-MSC) and age-matched healthy donors (HD-MSC) in order to identify a specific FL-MSC signature. In addition, we used Affymetrix microarrays to define the gene expression signature of lymphoid-like stromal cells obtained from HD-MSC by treatment with TNF/LT in vitro. This TNF/LT signature was then used to interpret the gene expression profile of FL-MSC. GEP was performed on 10 BM-MSC from FL patients and 6 from healthy donors, treated or not with TNF(10 ng/mL)/LT(100ng/mL)
Project description:In this series we have analyzed the effect of donor age on the gene expression profile of mesenchymal stromal cells (alternatively named mesenchymal stem cells; MSC) from human bone marrow. Cells were taken from bone marrow aspirates from iliac crest (BM) of healthy donors or from the caput femoris (HIP) of elderly patients that received femoral head prosthesis.
Project description:Tumor cells can induce their own advantageous microenvironment. Here, we describe aberrant cathepsin S (CTSS) activity to modulate T-cell activation in follicular lymphoma (FL). In donor-derived FLs following bone marrow transplantation, we identified independent acquisition of CTSS mutations at Y132 in the donor´s and recipient's tumors. In a larger cohort, 6% of FL (20/312) harbored CTSS mutations, mostly Y132D, another 14% had CTSS amplification (40/280). Y132D leads to accelerated conversion from pro-CTSS to active CTSS and increased substrate cleavage, including CD74, which regulates MHC-II restricted antigen-presentation. In co-culture experiments, CTSS mutant lymphoma cells induced increased antigen-specific CD4+ T-cell activation. Moreover, antigen-processing was the top upregulated pathway in CTSS mutant primary FL biopsies. Thus, aberrant CTSS activity is a promising target in lymphoma.
Project description:Tumor infiltrating neutrophils (TAN) have been shown to exert both pro- and anti-tumoral activities and their recruitment and polarization are triggered by tumor-derived signals. Resident mesenchymal stromal cells (MSC) could contribute to tumor-supportive cell niche and have been shown to display tumor-specific transcriptomic, phenotypic, and functional features compared to normal tissue. In our study, we investigate whether these two cell subsets establish a bidirectional crosstalk in the context of B-cell lymphoma. We used microarrays to explore how neutrophils could trigger the polarization of tumor-supportive stromal cells. Gene expression analysis were performed on stromal cells (MSC) derived from bone marrow (BM) or tonsil (Resto) of healthy donors. These BM-MSC (n=3) or Resto (n=3) were primed or not with neutrophils for 1 day to induce stromal modification.
Project description:Head Neck Squamous Cell Carcinoma (HNSCC)- or Bone Marrow (BM)- derived mesenchymal stromal cells (MSC) were analyzed either resting or following stimulation with IFN-g and TNF-a cytokines.
Project description:Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is not known. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as hESC by transcriptomics (RNA-Seq) and quantitative proteomics (nano LC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. A particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC.
