Blood platelet formation at a glance

Abstract

The main function of blood platelets is to ensure hemostasis and prevent hemorrhages. The 1011 platelets needed daily are produced in a well-orchestrated process. However, this process is not yet fully understood and in vitro platelet production is still inefficient. Platelets are produced in the bone marrow by megakaryocytes, highly specialized precursor cells that extend cytoplasmic projections called proplatelets (PPTs) through the endothelial barrier of sinusoid vessels. In this Cell Science at a Glance article and the accompanying poster we discuss the mechanisms and pathways involved in megakaryopoiesis and platelet formation processes. We especially address the – still underestimated – role of the microenvironment of the bone marrow, and present recent findings on how PPT extension in vivo differs from that in vitro and entails different mechanisms. Finally, we recapitulate old but recently revisited evidence that – although bone marrow does produce megakaryocytes and PPTs – remodeling and the release of bona fide platelets, mainly occur in the downstream microcirculation.

Microthrombocytopenia caused by impaired microtubule stability in RhoB-deficient mice

“…The different steps of platelet biogenesis highly depend on rearrangements of both the microtubule (MT) and actin cytoskeletal network. 1,2,8 Consistently, genetic defects impairing cytoskeletal dynamics can result in thrombocytopenia in humans and mice. 9 Rho GTPases act as molecular switches by cycling between an inactive guanosine diphosphate (GDP)-bound and an active guanosine triphosphate (GTP)-bound state.…”

“…Platelet biogenesis is a complex cellular process, 1,2 initiated by mature MKs in direct contact with the BM sinusoids, 3 and involves the penetration of endothelial cells, 4,5 and the extension of large cytoplasmic protrusions into the sinusoidal lumen, 6,7 which are shed and undergo maturation in the peripheral circulation to become bona fide platelets. The different steps of platelet biogenesis highly depend on rearrangements of both the microtubule (MT) and actin cytoskeletal network.…”

Iron and platelets: A subtle, under‐recognized relationship

“…According to the classical view of hematopoiesis, thrombopoietin controls megakaryopoiesis and thrombopoiesis 18 and platelets originate from bipotent megakaryocytic/erythroid progenitors (MEPs) 4,19 . Several genetic or acquired factors, independent of thrombopoietin, 20 direct the lineage commitment of MEPs toward either megakaryocyte progenitors (MkPs) or erythroid progenitors (ErPs).…”

“…Platelets (or thrombocytes) are cytoplasmic fragments derived from bone marrow megakaryocytes and produced at a daily rate of approximately 10 11 . 3,4 Once released into the plasma, they circulate, at a concentration of 150-400 Â 10 9 /L, and have a physiological lifespan of approximately seven to ten days. They undergo progressive senescence, particularly marked by desialylation of the platelet surface glycoproteins 5 before being cleared by the macrophagic system, especially in the spleen and liver.…”

Role of Rho-GTPases in megakaryopoiesis

“…Microtubule organization is also different with heterogeneously distributed microtubules in vivo whereas they form thick arrays all along the proplatelet in vitro [ 27 , 28 ]. The role of microtubules as a power for elongation seems less important in vivo than in vitro with actin rich shoulders being also involved in the extension of the proplatelet [ 34 , 35 ]. However a recent study suggests that only a minority of adult bone marrow MKs underwent proplatelet formation.…”