Megakaryocytes are large, specialized cells in the bone marrow, accounting for only one in every 10,000 bone marrow cells. They measure 50 to 100 micrometers in diameter, 10 to 15 times larger than a typical red blood cell. Their name, meaning ‘large nucleus cell’, refers to a prominent, multi-lobed nucleus that results from their unique development.
The Role of Megakaryocytes in the Body
The primary purpose of a megakaryocyte is producing platelets, a process called thrombopoiesis. Platelets are small, anuclear fragments that break off from the megakaryocyte’s cytoplasm. A single megakaryocyte can generate between 1,000 and 3,000 platelets, which is necessary to maintain the body’s circulating platelet count of 150,000 to 450,000 per microliter of blood.
To release platelets, a mature megakaryocyte migrates next to the bone marrow’s blood vessels, or sinusoids. The cell then extends long, branching cytoplasmic projections called proplatelets through the vessel walls and into the flowing blood. These proplatelets contain tandem arrays of platelet-sized swellings connected by thin cytoplasmic bridges, functioning as assembly lines for platelet creation.
The force of blood flow within the sinusoids shears these proplatelet extensions, causing them to fragment into individual platelets. The entire cytoplasm of the megakaryocyte is consumed in this process, and its leftover nucleus is cleared by other bone marrow cells. Platelets play a part in hemostasis, the process that stops bleeding at the site of an injury.
Development and Maturation
The development of megakaryocytes, a process called megakaryopoiesis, originates from hematopoietic stem cells in the bone marrow. These stem cells can differentiate into any blood cell, and their path to becoming a megakaryocyte is directed by molecular signals. The primary signal is the hormone thrombopoietin (TPO), which binds to receptors on progenitor cells, initiating internal signals that guide maturation.
A defining feature of megakaryocyte development is endomitosis. During this process, the cell replicates its DNA multiple times but does not divide. This results in a single cell with a large, lobulated nucleus containing multiple copies of its chromosomes, a state known as polyploidy. This increased genetic content supports the protein and membrane synthesis required to produce thousands of platelets.
As the megakaryocyte matures, it develops an extensive internal membrane network to build the proplatelet extensions. The journey from a committed stem cell to a mature, platelet-shedding megakaryocyte takes approximately four to seven days in humans, ensuring a steady supply of platelets.
Associated Medical Conditions
Disruptions in megakaryocyte number or function can lead to health issues related to abnormal platelet counts. When bone marrow fails to produce enough platelets, the condition is known as thrombocytopenia. This can be caused by factors that damage megakaryocytes, such as viral infections, toxic chemicals, or radiation therapy. In some cases, the body’s immune system attacks megakaryocytes, a condition called immune thrombocytopenia (ITP), which impairs their maturation and ability to form proplatelets.
Conversely, an overproduction of platelets leads to a condition called thrombocytosis. This is often the result of a myeloproliferative neoplasm, a blood cancer where bone marrow cells grow abnormally. One such condition is essential thrombocythemia (ET), characterized by the sustained overproduction of platelets from abnormal megakaryocytes. In ET, these cells are more sensitive to growth factors, leading to uncontrolled proliferation.
In many cases of essential thrombocythemia, mutations are found in genes like JAK2, CALR, or MPL. These mutations can cause signaling pathways to be permanently switched on, leading to excessive production of megakaryocytes and platelets. The high number of platelets in thrombocytosis increases the risk of forming unnecessary blood clots, which can lead to complications like stroke or heart attack.