Project description:N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated cation channels with high calcium permeability. Their activity supports megakaryocytes proliferation and maturation, however their downstream effects on the megakaryocyte transcriptome remain poorly elucidated. We used Clariom S Pico Arrays to profile the transcriptome changes caused by loss of Grin1 in mouse bone marrow megakaryocytes.
Project description:Megakaryocytes are bone marrow (BM) resident cells that derive from hematopoietic stem cells. A pivotal function of megakaryocytes is the generation of platelets through the release of long protrusions called proplatelets into sinusoidal vessels. single-cell RNA-sequencing on murine BM megakaryocytes has previously revealed transcriptional heterogeneity with segmentation into four distinct categories. These studies postulated functions beyond platelet production with evidence for immunoregulatory and stem cell niche supporting subtypes, as well as a cycling population. The spatial context and transcriptional heterogeneity of megakaryocytes is of great interest as localization of for instance the vasculature is a necessity for platelet production. For single-cell RNA sequencing this spatial orientation is however lost due to the dissociation of tissues. Recent technological advances have enabled the interrogation of gene expression profiles of tissues in situ. This enables the integration of morphological, situational and transcriptional information to classify cells in the context of their microenvironment. In the following we present, for the first time, the application of this technology to BM megakaryocytes at a single cell level.
Project description:Thrombocytopenia is a major and fatal complication for AML, while what happened to megakaryopoiesis and thrombopoiesis in AML remains unknown. Megakaryocytes have been recognized as essential HSC niche cells for their function to maintain HSC quiescence and support HSC regeneration. Megakaryocytes are robustly affected in AML bone marrow, while the alterations of their platelet-releasing and HSC supportive function are incompletely understood.
Project description:Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet production and phenotypes of resultant platelets. Here, we showed during sepsis that the spleen is a major site of megakaryopoiesis and platelet production. Sepsis provoked an adrenergic-dependent mobilization of megakaryocyte-erythrocyte progenitors (MEPs) from the bone marrow to the spleen where interleukin-3 (IL-3) induced their differentiation into megakaryocytes. In the spleen, immune-skewed megakaryocytes produced a CD40L-high platelet population with potent immunomodulatory functions. Transfusions of post-sepsis platelets enriched from splenic production enhanced immune responses and reduced overall mortality in sepsis-challenged animals. These findings identify a spleen-derived protective platelet population that may be broadly immunomodulatory in acute inflammatory states such as sepsis.
Project description:Transcriptional profiling of mouse bone marrow derived macrophages comparing wildtype with CDK5R1 knockout. CDK5R1 is an activating parter for CDK5 and synthesized upon TLRs stimaultion. Activated CDK5 has various target substrates, and functions as a key singnaling regulator in macrophages.
Project description:RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have hematologic cancer.
Project description:In this dataset, we determine the global gene expression in human induced pluripotent stem (iPS) cell-derived CD61+ megakaryocytes carrying homozygous JAK2 V617F mutation or the JAK2 wildtype gene.
Project description:Transcriptional profiling of mouse bone marrow derived macrophages comparing wildtype with CDK5R1 knockout. CDK5R1 is an activating parter for CDK5 and synthesized upon TLRs stimaultion. Activated CDK5 has various target substrates, and functions as a key singnaling regulator in macrophages. Two condition experiments: basal state and LPS-stimulated macrophages for 6 hours. Two biological replicates.