Thrombopoietin plays a role in inducing the megakaryocyte to form small proto-platelet processes. The cell ceases its growth at 4N, 8N or 16N, becomes granular, and begins to produce platelets. The maturation process occurs via endomitotic synchronous replication whereby the cytoplasmic volume enlarges as the number of chromosomes multiplies without cellular division. Once the cell has completed differentiation and become a mature megakaryocyte, it begins the process of producing platelets.

Many of the morphological features of megakaryocyte differentiation can be recapitulated in non-hematopoietic cells by the expression of Class VI β-tubulin (β6) and they provide a mechanistic basis for understanding these changes. The cytoplasm continues to expand and the DNA amount can increase up to 64n in humans and 256n in mice. However, it is still able to replicate its DNA and continue development, becoming polyploid. The cell eventually reaches megakaryocyte stage and loses its ability to divide. The megakaryocyte develops through the following lineage:ĬFU-Me ( pluripotential hemopoietic stem cell or hemocytoblast) → megakaryoblast → promegakaryocyte → megakaryocyte. Other molecular signals for megakaryocyte differentiation include GM-CSF, IL-3, IL-6, IL-11, chemokines ( SDF-1, FGF-4) and erythropoietin. TPO is sufficient but not absolutely necessary for inducing differentiation of progenitor cells in the bone marrow towards a final megakaryocyte phenotype. The primary signal for megakaryocyte production is thrombopoietin or TPO. These multipotent stem cells live in the marrow sinusoids and are capable of producing all types of blood cells depending on the signals they receive. They are produced primarily by the liver, kidney, spleen, and bone marrow. Megakaryocytes are derived from hematopoietic stem cell precursor cells in the bone marrow. The cytoplasm, just as the platelets that bud off from it, contains α-granula and dense bodies.

In some cases, the nucleus may contain up to 64N DNA, or 32 copies of the normal complement of DNA in a human cell. As a result, the nucleus of the megakaryocyte can become very large and lobulated, which, under a light microscope, can give the false impression that there are several nuclei. During its maturation, the megakaryocyte grows in size and replicates its DNA without cytokinesis in a process called endomitosis. In general, megakaryocytes are 10 to 15 times larger than a typical red blood cell, averaging 50–100 μm in diameter. Owing to variations in combining forms and spelling, synonyms include megalokaryocyte and megacaryocyte. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but can increase in number nearly 10-fold during the course of certain diseases. A megakaryocyte ( mega- + karyo- + -cyte, 'large-nucleus cell') is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes ( platelets), which are necessary for normal blood clotting.

Platelets are cell fragments.