Impact of<i>Itga2-Gp6</i>-double collagen receptor deficient mice for bone marrow megakaryocytes and platelets

Semeniak, Daniela; Faber, Kristina; Öftering, Patricia; Manukjan, Georgi; Schulze, Harald

doi:10.1101/625038

Cited by 3 publications

(1 citation statement)

References 35 publications

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“…81 In particular, megakaryocyte contact with type I collagen fibrils induces myosin light chain-2 (MLC-2) phosphorylation through the α2β1 integrin-dependent Rho-ROCK (Rho-associated protein kinase) pathway to regulate the cytoskeleton contractility, cell migration, and platelet release. 82 83 84 85 While, megakaryocyte interactions with fibrinogen, vitronectin, and fibronectin are mediated by αIIbβ3 integrin, which has a pivotal role regulating F-actin cytoskeleton during platelet biogenesis mainly through Fln-A interaction. 29 79 Mutations in the ITGA2B and ITGB3 genes cause Glanzmann thrombasthenia (GT), a bleeding disorder due to quantitative or qualitative defects of αIIbβ3 yielding reduced platelet aggregation while maintaining normal platelet count and size.…”

Section: Introductionmentioning

confidence: 99%

Megakaryocyte Cytoskeletal Proteins in Platelet Biogenesis and Diseases

2021

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Thrombopoiesis governs the formation of blood platelets in bone marrow by converting megakaryocytes into long, branched proplatelets on which individual platelets are assembled. The megakaryocyte cytoskeleton responds to multiple microenvironmental cues, including chemical and mechanical stimuli, sustaining the platelet shedding. During the megakaryocyte's life cycle, cytoskeletal networks organize cell shape and content, connect them physically and biochemically to the bone marrow vascular niche, and enable the release of platelets into the bloodstream. While the basic building blocks of the cytoskeleton have been studied extensively, new sets of cytoskeleton regulators have emerged as critical components of the dynamic protein network that supports platelet production. Understanding how the interaction of individual molecules of the cytoskeleton governs megakaryocyte behavior is essential to improve knowledge of platelet biogenesis and develop new therapeutic strategies for inherited thrombocytopenias caused by alterations in the cytoskeletal genes.

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Section: Introductionmentioning

confidence: 99%

Megakaryocyte Cytoskeletal Proteins in Platelet Biogenesis and Diseases

2021

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CXCL12-Abundant Reticular (CAR) Cells Direct Megakaryocyte Protrusions across the Bone Marrow Sinusoid Wall

Wagner

Mott

Upcin

et al. 2021

Cells

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Megakaryocytes (MKs) release platelets into the lumen of bone marrow (BM) sinusoids while remaining to reside within the BM. The morphogenetic events of this complex process are still not fully understood. We combined confocal laser scanning microscopy with transmission and serial block-face scanning electron microscopy followed by 3D-reconstruction on mouse BM tissue sections. These analyses revealed that MKs in close vicinity to BM sinusoid (BMS) wall first induce the lateral retraction of CXCL12-abundant reticular (CAR) cells (CAR), followed by basal lamina (BL) degradation enabling direct MK-sinusoidal endothelial cells (SECs) interaction. Subsequently, an endothelial engulfment starts that contains a large MK protrusion. Then, MK protrusions penetrate the SEC, transmigrate into the BMS lumen and form proplatelets that are in direct contact to the SEC surface. Furthermore, such processes are induced on several sites, as observed by 3D reconstructions. Our data demonstrate that MKs in interaction with CAR-cells actively induce BMS wall alterations, including CAR-cell retraction, BL degradation, and SEC engulfment containing a large MK protrusion. This results in SEC penetration enabling the migration of MK protrusion into the BMS lumen where proplatelets that are adherent to the luminal SEC surface are formed and contribute to platelet release into the blood circulation.

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Role of Nitric Oxide in Megakaryocyte Function

Asgari

Jurasz

2023

IJMS

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Megakaryocytes are the main members of the hematopoietic system responsible for regulating vascular homeostasis through their progeny platelets, which are generally known for maintaining hemostasis. Megakaryocytes are characterized as large polyploid cells that reside in the bone marrow but may also circulate in the vasculature. They are generated directly or through a multi-lineage commitment step from the most primitive progenitor or Hematopoietic Stem Cells (HSCs) in a process called “megakaryopoiesis”. Immature megakaryocytes enter a complicated development process defined as “thrombopoiesis” that ultimately results in the release of extended protrusions called proplatelets into bone marrow sinusoidal or lung microvessels. One of the main mediators that play an important modulatory role in hematopoiesis and hemostasis is nitric oxide (NO), a free radical gas produced by three isoforms of nitric oxide synthase within the mammalian cells. In this review, we summarize the effect of NO and its signaling on megakaryopoiesis and thrombopoiesis under both physiological and pathophysiological conditions.

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Impact ofItga2-Gp6-double collagen receptor deficient mice for bone marrow megakaryocytes and platelets

Cited by 3 publications

References 35 publications

Megakaryocyte Cytoskeletal Proteins in Platelet Biogenesis and Diseases

Megakaryocyte Cytoskeletal Proteins in Platelet Biogenesis and Diseases

CXCL12-Abundant Reticular (CAR) Cells Direct Megakaryocyte Protrusions across the Bone Marrow Sinusoid Wall

Role of Nitric Oxide in Megakaryocyte Function

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