The incredible journey: From megakaryocyte development to platelet formation

Abstract

Circulating blood platelets are specialized cells that prevent bleeding and minimize blood vessel injury. Large progenitor cells in the bone marrow called megakaryocytes (MKs) are the source of platelets. MKs release platelets through a series of fascinating cell biological events. During maturation, they become polyploid and accumulate massive amounts of protein and membrane. Then, in a cytoskeletal-driven process, they extend long branching processes, designated proplatelets, into sinusoidal blood vessels where they undergo fission to release platelets. Given the need for platelets in many pathological situations, understanding how this process occurs is an active area of research with important clinical applications.

Cytoskeletal regulation of platelet formation: Coordination of F-actin and microtubules

“…Platelets are produced from their progenitor cell, the megakaryocyte (MK), in the bone marrow in response to the hormone thromobopoietin (TPO) (Reviewed by Thon and Italiano 2012;Machlus and Italiano 2013). In response to TPO, haematopoietic stem cells differentiate into MKs by differential regulation/expression of transcription factors (including GATA1, FOG1, RUNX1, FLI1 and NF-E2).…”

Macrophage and Multinucleated Giant Cell Classification

“…This is in contrast to the mechanism of megakaryocyte formation. Megakaryocytes become polyploid by endomitosis, resulting in a single polylobulated nuclei with a histological appearance similar to MGC [73].…”

Genomics and transcriptomics of megakaryocytes and platelets: Implications for health and disease

“…Once in the circulation, platelets survive for ~7 to 10 days 5. Megakaryocytes produce ~100 billion platelets daily to maintain a normal range of circulating platelets of 150 to 400 000 platelets per microliter of blood 3. During this process, megakaryocytes distribute their transcriptome and splicing machinery into platelets (see Figure 1.1‐2) 2.…”

“…Megakaryocytes mostly mature in the bone marrow, developing their characteristic polyploidy as they undergo endomitosis, a process by which the cells replicate their DNA without completing cell division 13. During this maturation process, megakaryocytes increase their cytoplasmic volume and generate pro‐platelet extensions into the bone marrow sinusoids and shed platelets into the circulation 3. MEP lineages have been developmentally defined in human fetal liver and adult bone marrow.…”