Project description:A comparative single cell transcriptional analysis of murine CXCL12-abundant reticular stromal cells isolated from ablated and control bone marrow
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:A single cell transcriptomic profile of bone marrow stromal cells of the murine femur marked by Prrx1-cre at postnatal day 21 (P21)
Project description:A single cell transcriptomic profile of bone marrow stromal cells of the murine femur marked by Prrx1-cre at 18 months of age (18M)
Project description:We revealed a single cell transcriptional landscape of bone marrow mesenchymal stromal cells derived from the fetal growth plate cartilage
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:We identified CD73+ bone marrow stromal cells as hematopoietic niche candidates. To further validate our finding, we tested the functional role of CD73 during bone marrow transplantation using CD73-/- mice. We evaluated the transcriptome of transplanted WT hematopoietic stem and progenitor cells from WT or CD73-/- recipient mice and found changes in metabolic, cell cycle and signaling genes.