Project description:RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Scf; GFP+Cxcl12; DsRed+ bone marrow stromal cells ,2D cultured bone marrow stromal cells and 3D cultured bone marrow stromal cells. RNA sequencing data of sorted primary and 3D cocultured Lin-Sca1+C-kit+CD150+CD48+ hematopoietic stem cells from 8-12 weeks and 12-13 months old mice. RNA and ATAC sequencing data of primary sorting CD45-Ter119-CD31-Pdgfra+td-Tomato+ bone marrow stromal cells from young (8 wks), middle aged (12 months) and aged (22-24 months) Lepr-Cre;td-Tomato mice.
Project description:Examination of gene expression in FACS-purified Ter119- CD45- Chrna7+ bone marrow stromal cells as a function of B cell-derived acetylcholine
Project description:Bone marrow stromal cells are commonly defined by CD45–Ter119–CD31– (Triple-negative cells or TNCs). In this study, we show that most TNCs are not labeled by mesenchymal cell genetic labeling models but are derived from hematopoietic stem and progenitor cells. RNA-Seq analysis of TNCs reveals erythroid and lymphoid progenitor signatures among CD51– TNCs which was confirmed by in vitro culture studies with primary bone marrow stromal cells and by in vivo transplantation experiments. We also show that CD44+CD51– TNCs expands during phenylhydrazine-induced hemolytic anemia and in a mouse model of sickle cell disease. These results uncover new classes of stromal-associated hematopoietic progenitors.
Project description:Recent studies suggest that bone marrow stromal cells are critical for forming a niche that maintains hematopoietic stem cells’ quiescence and adapt blood production to the organism’s needs. Alterations in the bone marrow niche are commonly observed in blood malignancies and directly contribute to the aberrant function of disease-initiating leukemic stem cells. We used microarrays to detail the global programme of stromal cells' gene expression during leukemic progression.
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:In order to comprehensively characterize bone marrow mesenchymal cells after myeloablation, single-nuclei RNA sequencing was performed on bone marrow adipocytes and bone marrow stromal cells isolated from sublethally-irradiated mice.
Project description:Human bone marrow stromal cells (BMSCs) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key BMSC functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key BMSC regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSCs, downregulated upon culture, and lower in non-CFU-F-containing CD45neg BM cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSCs. Accordingly, EGR1 overexpression markedly decreased BMSC proliferation but considerably improved hematopoietic stroma support function as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement of BMSC stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. On the other hand, EGR1 knockdown increased ROS-mediated BMSC proliferation, and clearly reduced BMSC hematopoietic stroma support potential. These findings thus show that EGR1 is a key BMSC transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to coordinate the specific functions of BMSC in their different biological contexts.
Project description:Multiple myeloma is hematologic malignancies result from clonal proliferation of plasma cells. Recently, increasing evidence supports the hypothesis that microenvironment cells play important roles in the proliferation, survival, and drug resistance of clonal plasma cells. The aim of this study is to culture stromal cells from bone marrow aspirates of patients with multiple myeloma, and to investigate expression profiles of bone marrow stromal cells and their relationships with the clinical characteristics of patients. RNA was extracted cultured bone marrow stromal cells from 15 patients with plasma cell neoplasms, and bone marrow stromal cells from 13 control patients with 9 B-cell lymphoma patients with no evidence of BM involvement and 4 patients with mild-to-moderate cytopenia without evidence of hematologic malignancies