Disease relevance of Megakaryocytes

• Unexpectedly, NF-E2-/- mice lack circulating platelets and die of hemorrhage; their megakaryocytes show no cytoplasmic platelet formation [1].
• Initial data suggest that megakaryocyte production is stimulated by a factor detectable in aplastic anemia serum that may be distinct from other known hematopoietic stem cell regulators [2].
• VASP-/- mice demonstrated hyperplasia of megakaryocytes in bone marrow and spleen but exhibited no other macroscopic or microscopic abnormalities [3].
• Preliminary biological characterization indicates that in addition to stimulating plasmacytoma proliferation, IL-11 stimulates the T-cell-dependent development of immunoglobulin-producing B cells and synergizes with IL-3 in supporting murine megakaryocyte colony formation [4].
• Using the technique of thrombophoresis (TP), platelet and megakaryocyte dynamics following acute thrombocytopenia were studied in two normal subjects during periods of ethanol ingestion and abstinence [5].

Psychiatry related information on Megakaryocytes

• NACP, a synaptic protein involved in Alzheimer's disease, is differentially regulated during megakaryocyte differentiation [6].

High impact information on Megakaryocytes

• These studies demonstrate the importance of the Flt3 receptor tyrosine kinase as the earliest marker of hematopoietic cell fate commitment in that erythrocyte and megakaryocyte potentials are lost first as HSCs differentiate to lymphocyte progenitors [7].
• We present evidence for a population of cells which, although sustaining a high proliferative and combined lympho-myeloid differentiation potential, have lost the ability to adopt erythroid and megakaryocyte lineage fates [8].
• Thus, as an essential factor for megakaryocyte maturation and platelet production, NF-E2 must regulate critical target genes independent of the action of thrombopoietin [1].
• Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development [1].
• Identification and cloning of a megakaryocyte growth and development factor that is a ligand for the cytokine receptor Mpl [9].

Chemical compound and disease context of Megakaryocytes

• We previously used a retrovirus vector containing a cDNA cassette encoding human integrin beta3 to restore integrin alphaIIbbeta3 on the surface of megakaryocytes derived from peripheral blood stem cells of GT patients [10].
• It is concluded that the thrombocytosis that occurs after 5-fluorouracil originates from a class of primitive stem cells, or early megakaryocyte precursors, which are not killed by the drug [11].
• The digestion of 15% and 48% of megakaryocyte sialic acid with neuraminidase from Vibrio cholera resulted in a 67% and 89% decrease in the binding of rhodamine-WGA, respectively, as determined by microdensitometry [12].
• These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors [13].
• Macrothrombocytopenia with abnormal demarcation membranes in megakaryocytes and neutropenia with a complete lack of sialyl-Lewis-X antigen in leukocytes--a new syndrome [14]?

Biological context of Megakaryocytes

• In vivo, c-Mpl ligand stimulates platelet production by greatly expanding marrow and splenic megakaryocytes and their progenitors, and by shifting the distribution of megakaryocyte ploidy to higher values [15].
• AML-1 is thus required for maturation of megakaryocytes and differentiation of T and B cells, but not for maintenance of hematopoietic stem cells (HSCs) in adult hematopoiesis [16].
• After discontinuing GCV, the bone marrow was repopulated with megakaryocytes and the platelet count was restored within 7 d [17].
• This protection coincided with the finding that significantly more progenitors for colony-forming unit-culture (CFU-c) and CFU-granulocyte, erythroid, megakaryocyte, macrophage (GEMM) were removed from S-phase by TGF-beta in mice undergoing hematopoietic recovery than in normal mice [18].
• These results establish GM-CSF as a multilineage growth factor with definite megakaryocyte colony-stimulating activity and indicate that both GM-CSF and IL-3 are important in the regulation of megakaryocytopoiesis [19].

Anatomical context of Megakaryocytes

• Canine MGDF and recombinant human MGDF support the development of megakaryocytes from human CD34+ progenitor cell populations in liquid culture and promote the survival of a factor-dependent murine cell line (32D) engineered to express MpI [9].
• Using in situ hybridization of mouse bone marrow cells and northern blot analysis of purified cell populations and permanent cell lines, we show here that GF-1 is expressed in two other hematopoietic lineages, megakaryocytes and bone marrow-derived mast cells [20].
• The haematopoietic growth factor known as granulocyte-monocyte colony-stimulating factor (GM-CSF) has the ability to stimulate proliferation and differentiation of normal granulocyte-monocyte and eosinophil stem cells and enhance the proliferation of pluripotent, megakaryocyte and erythroid stem cells [21].
• Common myeloid progenitors give rise to either megakaryocyte/erythrocyte or granulocyte/macrophage progenitors [22].
• Von Willebrand factor (vWF), a multifunctional haemostatic glycoprotein derived from endothelial cells and megakaryocytes, mediates platelet adhesion to injured subendothelium and binds coagulation factor VIII in the circulation [23].

Associations of Megakaryocytes with chemical compounds

• Here we report that estradiol synthesized in megakaryocytes triggers PPF [24].
• No reaction product was found in alpha-granules at any stage of megakaryocyte maturation, nor in alpha- or serotonin granules of platelets [25].
• Kistrin, an integrin antagonist, blocks endocytosis of fibrinogen into guinea pig megakaryocyte and platelet alpha-granules [26].
• By immunoperoxidase staining monocyte-macrophage protein seems to be localized in the cytoplasm, similar to the known cytoplasmic distribution of platelet and megakaryocyte Factor XIII [27].
• 1,25-(OH)2D3 inhibits the proliferation of megakaryocytes which normally promote collagen synthesis [28].

Gene context of Megakaryocytes

• One is a megakaryocyte-colony stimulating factor (MK-CSF) which induces the proliferation and differentiation of megakaryocyte progenitors, and the second, thrombopoietin, is a megakaryocyte maturation factor [29].
• This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages [30].
• The c-mpl-/- mice had an 85 percent decrease in their number of platelets and megakaryocytes but had normal amounts of other hematopoietic cell types [31].
• Accordingly, absence of Tel/Etv6 after lineage commitment is ostensibly without consequence except for unexpected impairment of maturation of megakaryocytes [32].
• Transendothelial migration of megakaryocytes in response to stromal cell-derived factor 1 (SDF-1) enhances platelet formation [33].

Analytical, diagnostic and therapeutic context of Megakaryocytes

• Analysis of various platelet proteins by immunofluorescence demonstrated that platelet glycoproteins Ib, IIb, and IIIa, as well as plasma factor VIII antigen (factor VIII:AGN), platelet factor 4, and fibronectin are present in the vast majority of morphologically recognizable megakaryocytes [34].
• Light microscopic immunocytochemistry demonstrated multimerin in normal megakaryocytes and in Dami cells after stimulation with PMA [35].
• Microinjection of PI3,4, 5P(3) into megakaryocytes caused a 3-fold increase in Ca(2+) in response to CRP, which was absent in X-linked immunodeficiency (Xid) mice, which have a mutation in the PH domain of Btk [36].
• We had the opportunity to reexamine megakaryocytes from a patient with acute promyelocytic leukemia (M3), after chemotherapy [37].
• In normal murine marrow-derived progenitors analyzed by single-cell reverse transcription-polymerase chain reaction (RT-PCR), ski expression is limited to dual-lineage megakaryocyte/erythrocyte colony-starts [38].

References