Use of electron microscopy to study megakaryocytes

Scandola, Cyril; Erhardt, Mathieu; Rinckel, Jean‐Yves; Proamer, Fabienne; Gachet, Christian; Eckly, Anita

doi:10.1080/09537104.2019.1708885

Cited by 6 publications

(1 citation statement)

References 52 publications

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“…Morphology is an important parameter of MKs that can be obtained by immunohistology or immunofluorescence. Electron microscopy can be used to evaluate the identity and maturation status of MKs, the platelet-producing MKs usually presenting a large nucleus with a well-developed cytoplasm displaying demarcation membranes and numerous alpha-granules ( 113 ), as it has been shown for MKs retrieved from human pulmonary arteries ( 81 ). The ability of MKs to produce platelets is the final proof of MK identity and can be studied in vitro using flow chamber devices to mimic a more natural environment, but the dynamics of platelet formation can only be investigated since the development of two-photon microscopy ( 116 ).…”

Section: Mk Identity and Methodology Advices For Further Studiesmentioning

confidence: 99%

Occurrence and role of lung megakaryocytes in infection and inflammation

2022

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Megakaryocytes (MKs) are large cells giving rise to platelets. It is well established that in adults, MKs develop from hematopoietic stem cells and reside in the bone marrow. MKs are also rare but normal constituents of the venous blood returning to the lungs, and MKs are found in the lung vasculature (MKcirc), suggesting that these cells are migrants from the bone marrow and get trapped in lung capillaries where the final steps of platelet production can occur. An unprecedented increase in the number of lung and circulating MKs was described in coronavirus disease 2019 (COVID-19) patients, suggesting that lung thrombopoiesis may be increased during lung infection and/or thromboinflammation. In addition to the population of platelet-producing intravascular MKs in the lung, a population of lung-resident megakaryocytes (MKL) has been identified and presents a specific immune signature compared to its bone marrow counterparts. Recent single-cell analysis and intravital imaging have helped us gain a better understanding of these populations in mouse and human. This review aims at summarizing the recent data on increased occurrence of lung MKs and discusses their origin, specificities, and potential role in homeostasis and inflammatory and infectious lung diseases. Here, we address remaining questions, controversies, and methodologic challenges for further studies of both MKcirc and MKL.

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Section: Mk Identity and Methodology Advices For Further Studiesmentioning

confidence: 99%

Occurrence and role of lung megakaryocytes in infection and inflammation

2022

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Mechanical confinement prevents ectopic platelet release

Guinard,

Brassard-Jollive,

Ruch

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Blood platelets are produced by megakaryocytes (MKs), their parent cells, which are in the bone marrow. Once mature, MK pierces through the sinusoid vessel, and the initial protrusion further elongates as proplatelet or buds to release platelets. The mechanisms controlling the decision to initiate proplatelet and platelet formation are unknown. Here, we show that the mechanical properties of the microenvironment prevent proplatelet and platelet release in the marrow stroma while allowing this process in the bloodstream. Loss of marrow confinement following myelosuppression led to inappropriate proplatelet and platelet release into the extravascular space. We further used an inert viscoelastic hydrogel to evaluate the impact of compressive stress. Transcriptional analysis showed that culture in three-dimensional gel induced upregulation of genes related to the Rho-GTPase pathway. We found higher Rho-GTPase activation, myosin light chain phosphorylation and F-actin under mechanical constraints while proplatelet formation was inhibited. The use of latrunculin-A to decrease F-actin promoted microtubule-dependent budding and proplatelet extension inside the gel. Additionally, ex vivo exposure of intact bone marrow to latrunculin-A triggered proplatelet extensions in the interstitial space. In vivo, this confinement-mediated high intracellular tension is responsible for the formation of the peripheral zone, a unique actin-rich structure. Cytoskeleton reorganization induces the disappearance of the peripheral zone upon reaching a liquid milieu to facilitate proplatelet and platelet formation. Hence, our data provide insight into the mechanisms preventing ectopic platelet release in the marrow stroma. Identifying such pathways is especially important for understanding pathologies altering marrow mechanics such as chemotherapy or myelofibrosis.

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Super-resolution imaging and quantification of megakaryocytes and platelets

Khan

Pike

2020

Platelets

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Use of electron microscopy to study megakaryocytes

Cited by 6 publications

References 52 publications

Occurrence and role of lung megakaryocytes in infection and inflammation

Occurrence and role of lung megakaryocytes in infection and inflammation

Mechanical confinement prevents ectopic platelet release

Super-resolution imaging and quantification of megakaryocytes and platelets

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