Project description:Focal lesions of articular cartilage give rise to pain and reduced joint function and may, if left untreated, lead to osteoarthritis. Implantation of in vitro generated, scaffold-free autologous cartilage discs may represent the best treatment option. Here we compare articular chondrocytes (ACs) and bone marrow-derived mesenchymal stromal cells (MSCs) for their ability to make scaffold-free cartilage discs.
Project description:We revealed a single cell transcriptional landscape of bone marrow mesenchymal stromal cells derived from the fetal growth plate cartilage
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: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:Global expression profile of human osteoblast treated with chemotherapy-treated bone marrow stromal cell conditioned media, compared to human osteoblast cells treated with diluent-control bone marrow stromal cell conditioned media. Goal is to identify genes regulated by chemotherapy in osteoblasts.
Project description:The bone marrow microenvironment is composed of heterogeneous cell populations of non-hematopoietic cells with complex phenotypes and undefined trajectories of maturation. Among them, mesenchymal cells maintain the production of stromal, bone, fat and cartilage cells. Resolving these unique cellular subsets within the bone marrow remains challenging. Here, we used single-cell RNA-sequencing of non-hematopoietic bone marrow cells to define specific subpopulations. Furthermore, by combining computational prediction of the cell state hierarchy with known expression of key transcription factors, we mapped differentiation paths to the osteocyte, chondrocyte, and adipocyte lineages. Finally, we validated our findings using lineage-specific reporter strains and targeted knockdowns. Our analysis reveals differentiation hierarchies for maturing stromal cells, determines key transcription factors along these trajectories, and provides an understanding of the complexity of the bone marrow microenvironment.
Project description:Our goal was to determine whether osteoblastic LuCaP 23.1 prostate cancer xenograft tumors can elicit an osteoblastic response at the gene expression level in human bone marrow stromal cells.