Project description:Mesenchymal stromal cells are a critical component of the bone marrow hematopoietic stem cell niche. In myelofibrosis, these cells are the major source of fibrosis in the bone marrow. We performed gene expression analysis using microarrays to systematically elucidate the mechanisms leading to fibrogenic conversion of these cells.
Project description:Expression analysis of migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow Keywords: fetal bone marrow, mesenchymal stromal cells, migration, gene expression, genomics Three biological replates for both migrating and non-migrating mesenchymal stromal cells (MSC) in fetal bone marrow
Project description:In order to comprehensively characterize the cellular constituents of the bone marrow microenvironment in primary myelofibrosis, single-cell RNA sequencing was performed on bone marrow stromal cells isolated from mice transplanted with MPLW515L-transduced hematopoietic cells.
Project description:Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity is attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironment. Within these niches, Mesenchymal Stromal Cells (BM-MSC) play a supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic progenitors. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic progenitor deregulation that features PMF. Primary Myelofibrosis, mesenchymal stroma cells, bone marrow, myeloproliferative disorders Transcriptome analysis was performed on BM-MSC amplified in vitro after 3 to 5 passages. Agilent Whole Human Genome Oligo Microarrays were used to compare expression profiling of BM-MSC from PMF patients and healthy donors.
Project description:Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity is attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironment. Within these niches, Mesenchymal Stromal Cells (BM-MSC) play a supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic progenitors. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic progenitor deregulation that features PMF. Primary Myelofibrosis, mesenchymal stroma cells, bone marrow, myeloproliferative disorders
Project description:TGF-β regulates fetale bone marrow niche emergence. Abrogating TGF-β signaling in mesenchymal cells during development results in a marked expansion of adipocytes and CAR cells in the bone marrow, while osteoblasts are reduced. RNA expression data from Osx-Cre targeted mesenchymal stromal cells obtained from E16.5 mouse hindlimbs of transgenic mice lacking Tgfbr2 in mesenchymal stromal cells or littermate controls.
