megakaryocyte differentiation
Definition
Target type: biologicalprocess
The process in which a myeloid precursor cell acquires specializes features of a megakaryocyte. [GOC:mah]
Megakaryocyte differentiation is a complex and tightly regulated process that involves a series of steps, ultimately leading to the formation of mature megakaryocytes, large polyploid cells responsible for producing platelets. This process begins with a committed hematopoietic progenitor cell known as a megakaryocyte progenitor (MKP). MKPs undergo a series of divisions and maturation steps under the influence of various cytokines and growth factors, including thrombopoietin (TPO).
During differentiation, MKPs undergo endomitosis, a unique process characterized by repeated rounds of DNA replication without cell division. This results in a dramatic increase in cell size and ploidy, with the nucleus becoming highly lobulated and the cytoplasm expanding significantly. This expansion is accompanied by the production of α-granules, dense granules, and other specialized organelles that are essential for platelet function.
As MKPs mature into megakaryocytes, they migrate from the bone marrow to the vascular sinuses, where they extend proplatelet processes, long, thin projections that extend into the bloodstream. These proplatelets then fragment into platelets, small anucleate cells that play a crucial role in hemostasis, the process that stops bleeding.
Key features of megakaryocyte differentiation include:
* **Commitment:** MKPs commit to the megakaryocyte lineage under the influence of TPO and other signaling molecules.
* **Endomitosis:** Repeated rounds of DNA replication without cell division, leading to polyploidy.
* **Cytoplasmic maturation:** Expansion of the cytoplasm and production of α-granules, dense granules, and other organelles.
* **Proplatelet formation:** Extension of proplatelet processes into the bloodstream.
* **Platelet release:** Fragmentation of proplatelets into platelets.
The regulation of megakaryocyte differentiation is a complex process involving a network of transcription factors, signaling pathways, and epigenetic modifications. Several transcription factors, including GATA1, NF-E2, and RUNX1, play critical roles in this process. Disruptions in any of these steps can lead to megakaryocyte dysfunction and platelet disorders.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Flavin reductase (NADPH) | A flavin reductase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P30043] | Homo sapiens (human) |
Compounds (7)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| erythrosine | Fluoresceins: A family of spiro(isobenzofuran-1(3H),9'-(9H)xanthen)-3-one derivatives. These are used as dyes, as indicators for various metals, and as fluorescent labels in immunoassays. | ||
| sulfasalazine | sulfasalazine : An azobenzene consisting of diphenyldiazene having a carboxy substituent at the 4-position, a hydroxy substituent at the 3-position and a 2-pyridylaminosulphonyl substituent at the 4'-position. Sulfasalazine: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907) | ||
| olsalazine | olsalazine : An azobenzene that consists of two molecules of 4-aminosalicylic acid joined by an azo linkage. A prodrug for mesalazine, an anti-inflammatory drug, it is used (as the disodium salt) in the treatment of inflammatory bowel disease. olsalazine: cpd with 2 salicylate molecules linked together by an azo bond | azobenzenes; dicarboxylic acid | non-steroidal anti-inflammatory drug; prodrug |
| tamibarotene | tamibarotene : A dicarboxylic acid monoamide resulting from the condensation of one of the carboxy groups of terephthalic acid with the amino group of 5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-amine. tamibarotene: has retinoid-binding activity | dicarboxylic acid monoamide; retinoid; tetralins | antineoplastic agent; retinoic acid receptor alpha/beta agonist |
| febuxostat | febuxostat : A 1,3-thiazolemonocarboxylic acid that is 4-methyl-1,3-thiazole-5-carboxylic acid which is substituted by a 3-cyano-4-(2-methylpropoxy)phenyl group at position 2. It is an orally-active, potent, and selective xanthine oxidase inhibitor used for the treatment of chronic hyperuricaemia in patients with gout. Febuxostat: A thiazole derivative and inhibitor of XANTHINE OXIDASE that is used for the treatment of HYPERURICEMIA in patients with chronic GOUT. | 1,3-thiazolemonocarboxylic acid; aromatic ether; nitrile | EC 1.17.3.2 (xanthine oxidase) inhibitor |
| deferasirox | deferasirox : A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions. Deferasirox: A triazole and benzoate derivative that acts as a selective iron chelator. It is used in the management of chronic IRON OVERLOAD due to blood transfusion or non-transfusion dependent THALASSEMIA. | benzoic acids; monocarboxylic acid; phenols; triazoles | iron chelator |
| ptc 124 | oxadiazole; ring assembly |