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Megakaryocytes

Megakaryocytes Background

Available Resources for Megakaryocyte Study

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About Megakaryocytes

Megakaryocytes are among the largest cells in the bone marrow, ranging in size from 30 to 100 micrometers in diameter. They have a distinctive appearance characterized by a large, lobulated nucleus and abundant cytoplasm. Within the cytoplasm, there is a network of tubular structures called demarcation membranes, which form the basis for platelet production. These membranes extend into proplatelets, long cytoplasmic extensions that protrude into the blood vessels, where platelets are eventually formed.

Megakaryocytes develop from hematopoietic stem cells in a multistep process known as megakaryopoiesis. Under the influence of specific growth factors, such as thrombopoietin (TPO), stem cells differentiate into megakaryocyte-erythroid progenitors (MEPs). These progenitors then give rise to megakaryocyte-committed progenitors, which mature into megakaryocytes.

During maturation, megakaryocytes undergo a unique process called endomitosis. Instead of undergoing cell division, they replicate their DNA multiple times without undergoing cytokinesis, resulting in a polyploid nucleus with 8N to 64N DNA content. The increased DNA content enables megakaryocytes to produce large amounts of platelets.

Megakaryocyte development from HSC to platelet.Fig.1 Megakaryocyte development from HSC to platelet. (Cunin P, et al., 2019)

HSC give rise to the common myeloid progenitor (CMP), MK-erythrocyte progenitor (MEP), and the lineage-committed megakaryocyte precursor (MkP). The HSC compartment also contains stem-like MK-committed progenitors (SL-MkP), remaining quiescent at steady state but rapidly giving rise to MkP during inflammation. After multiple round of endomitosis, MkP become mature MKs and release platelets into bone marrow sinusoids or migrate to the lung vasculature, where platelet production continues through the development of proplatelets. Under acute inflammatory or cytopenic conditions, elevation of IL-1α level promotes platelet release through rapid subdivision of the MK cytoplasm into platelets ("MK rupture"). In blue: characteristic surface markers during megakaryocyte ontogeny in mouse.

Role and Functions of Megakaryocytes

  • Platelet Production: The primary function of megakaryocytes is to produce platelets. As megakaryocytes mature, they extend long, branching cytoplasmic processes called proplatelets into the sinusoidal blood vessels of the bone marrow. These proplatelets undergo fragmentation, forming numerous platelets that are released into the bloodstream. Platelets are small, disc-shaped cell fragments that circulate in the blood. They play a crucial role in hemostasis, which is the process of preventing blood loss from damaged blood vessels. Platelets adhere to the site of injury, aggregate together, and form a plug to stop bleeding.
  • Thrombopoiesis Regulation: The production and release of platelets from megakaryocytes are tightly regulated by various factors. Thrombopoietin (TPO) is the primary regulator of megakaryocyte development. It is a hormone produced in the liver and kidneys that stimulates the differentiation, proliferation, and maturation of megakaryocytes. TPO binds to its receptor, c-Mpl, on the surface of megakaryocytes, and activates signaling pathways that promote their maturation and platelet production.
  • Interaction with Bone Marrow Microenvironment: Megakaryocytes interact with other cells in the bone marrow microenvironment, such as osteoblasts and endothelial cells. Osteoblasts provide physical support and signaling molecules necessary for megakaryocyte development and platelet production. Endothelial cells, which line the blood vessels, also play a role in megakaryocyte maturation and platelet release.
  • Inflammation: Megakaryocytes release pro-inflammatory mediators, interact with immune cells, and contribute to platelet-mediated inflammation, thereby influencing the overall inflammatory response. Additionally, they possess immunomodulatory properties, participate in tissue repair and angiogenesis, and engage in crosstalk with stromal cells, further impacting the inflammatory processes. Overall, megakaryocytes are key players in inflammation, modulating immune responses and contributing to tissue repair and remodeling.

Release of Bioactive Molecules: Megakaryocytes can release various bioactive molecules, such as cytokines, growth factors, and extracellular vesicles. These molecules can influence immune responses, inflammation, and tissue repair processes. For example, megakaryocytes can release platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF), which promote blood vessel formation and tissue repair.

Megakaryocyte effector mechanisms. Fig.2 Megakaryocyte effector mechanisms. (Cunin P, et al., 2019)

References:

  1. Malara A, Abbonante V, Di Buduo CA, Tozzi L, Currao M, Balduini A. The secret life of a megakaryocyte: emerging roles in bone marrow homeostasis control. Cell Mol Life Sci. 2015;72(8):1517-1536. doi:10.1007/s00018-014-1813-y
  2. Cunin P, Nigrovic PA. Megakaryocytes as immune cells. J Leukoc Biol. 2019;105(6):1111-1121. doi:10.1002/JLB.MR0718-261RR
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