FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2911451279> ?p ?o ?g. }

• W2911451279 endingPage "23" @default.
• W2911451279 startingPage "SCI" @default.
• W2911451279 abstract "Abstract Blood platelets play key roles in hemostasis and thrombosis and are the second most abundant cell type in the circulation. Due to their short life span of only a few days, anuclear platelets are continuously replenished and thus provide a classic system to study hematopoiesis. In mammals, platelets are produced by megakaryocytes (MKs) that are predominantly residing in the bone marrow (BM). MKs originate from hematopoietic stem cells and are thought to migrate from an endosteal niche towards the vascular sinusoids during their maturation. Unfortunately, previous studies on megakaryopoiesis were often limited by 2D imaging and cutting artefacts when analyzing bone sections, potentially resulting in underestimation of MK-to-vessel contacts and MK volumes. We studied megakaryopoiesis by visualizing MKs in their 3D environment. To this end, murine bones were simultaneously stained for MKs and endothelial cells, fixed, chemically cleared and imaged by Light Sheet Fluorescence Microscopy (LSFM). Thus, we achieved 3D-reconstructions of the complete and intact bone with subcellular resolution. Through imaging of MKs in the intact BM, we show that MKs can be found within the entire BM, without a bias towards bone-distant regions. We developed and compared different image processing pipelines and simulation scenarios for precise identification of MKs in 3D light-sheet fluorescence microscopy of uncut murine bones. By combining in vivo two-photon microscopy and in situ LSFM with computational simulations, we reveal surprisingly slow MK migration, limited intervascular space, and a vessel-biased MK pool. To complement limited imaging approaches computational simulations represent an important, well-controllable tool. Typically, simulation studies use artificial meshes as templates to minimize the computational effort or due to the lack of experimental data. Unfortunately, such simplified artificial templates for MKs and the vasculature can bias simulations and lead to misinterpretations as we show here. Using the segmented cell and vessel objects of true 3D images can overcome those limitations providing a simulation framework that has the prerequisites to maximally reflect the physiological situation. Thus, imaging and simulations go hand in hand when the respective 3D cell and vessel objects perfectly serve as biological templates for advanced simulations. We demonstrate reliable whole-bone analysis in silico, and found that MKs influence neutrophil and HSC migration as biomechanical restrainers modulating cell mobility and extravasation. These data challenge the current thrombopoiesis model of MK migration and support a modified model, where MKs at sinusoids are replenished by sinusoidal precursors rather than cells from a distant periostic niche (1). Furthermore, we identify MKs as biomechanical restraints for bone marrow cell mobilization. As MKs themselves do not need to migrate to reach the vessel, therapies to increase MK numbers might be sufficient to raise platelet counts. (1) Stegner D, van Eeuwijk JMM, Angay O, Gorelashvili MG, Semeniak D, Pinnecker J, Schmithausen P, Meyer I, Friedrich M, Dütting S, Brede C, Beilhack A, Schulze H, Nieswandt B, Heinze KG. Thrombopoiesis is spatially regulated by the bone marrow vasculature, Nat Commun. 2017 8(1):127. Figure. Figure. Disclosures No relevant conflicts of interest to declare." @default.
• W2911451279 created "2019-02-21" @default.
• W2911451279 creator A5008888080 @default.
• W2911451279 creator A5009263893 @default.
• W2911451279 creator A5015284985 @default.
• W2911451279 creator A5015314925 @default.
• W2911451279 creator A5019606440 @default.
• W2911451279 creator A5029864722 @default.
• W2911451279 creator A5031710910 @default.
• W2911451279 creator A5032588618 @default.
• W2911451279 creator A5063407801 @default.
• W2911451279 creator A5065710348 @default.
• W2911451279 creator A5069434242 @default.
• W2911451279 creator A5084781958 @default.
• W2911451279 creator A5091194864 @default.
• W2911451279 date "2018-11-29" @default.
• W2911451279 modified "2023-09-27" @default.
• W2911451279 title "Spatial Regulation of Thrombopoiesis in the Bone Marrow" @default.
• W2911451279 doi "https://doi.org/10.1182/blood-2018-99-109545" @default.
• W2911451279 hasPublicationYear "2018" @default.
• W2911451279 type Work @default.
• W2911451279 sameAs 2911451279 @default.
• W2911451279 citedByCount "0" @default.
• W2911451279 crossrefType "journal-article" @default.
• W2911451279 hasAuthorship W2911451279A5008888080 @default.
• W2911451279 hasAuthorship W2911451279A5009263893 @default.
• W2911451279 hasAuthorship W2911451279A5015284985 @default.
• W2911451279 hasAuthorship W2911451279A5015314925 @default.
• W2911451279 hasAuthorship W2911451279A5019606440 @default.
• W2911451279 hasAuthorship W2911451279A5029864722 @default.
• W2911451279 hasAuthorship W2911451279A5031710910 @default.
• W2911451279 hasAuthorship W2911451279A5032588618 @default.
• W2911451279 hasAuthorship W2911451279A5063407801 @default.
• W2911451279 hasAuthorship W2911451279A5065710348 @default.
• W2911451279 hasAuthorship W2911451279A5069434242 @default.
• W2911451279 hasAuthorship W2911451279A5084781958 @default.
• W2911451279 hasAuthorship W2911451279A5091194864 @default.
• W2911451279 hasConcept C105702510 @default.
• W2911451279 hasConcept C109159458 @default.
• W2911451279 hasConcept C142724271 @default.
• W2911451279 hasConcept C185592680 @default.
• W2911451279 hasConcept C203014093 @default.
• W2911451279 hasConcept C2776958478 @default.
• W2911451279 hasConcept C2779705218 @default.
• W2911451279 hasConcept C2780007613 @default.
• W2911451279 hasConcept C28328180 @default.
• W2911451279 hasConcept C71924100 @default.
• W2911451279 hasConcept C86803240 @default.
• W2911451279 hasConcept C89560881 @default.
• W2911451279 hasConcept C95444343 @default.
• W2911451279 hasConceptScore W2911451279C105702510 @default.
• W2911451279 hasConceptScore W2911451279C109159458 @default.
• W2911451279 hasConceptScore W2911451279C142724271 @default.
• W2911451279 hasConceptScore W2911451279C185592680 @default.
• W2911451279 hasConceptScore W2911451279C203014093 @default.
• W2911451279 hasConceptScore W2911451279C2776958478 @default.
• W2911451279 hasConceptScore W2911451279C2779705218 @default.
• W2911451279 hasConceptScore W2911451279C2780007613 @default.
• W2911451279 hasConceptScore W2911451279C28328180 @default.
• W2911451279 hasConceptScore W2911451279C71924100 @default.
• W2911451279 hasConceptScore W2911451279C86803240 @default.
• W2911451279 hasConceptScore W2911451279C89560881 @default.
• W2911451279 hasConceptScore W2911451279C95444343 @default.
• W2911451279 hasIssue "Supplement 1" @default.
• W2911451279 hasLocation W29114512791 @default.
• W2911451279 hasOpenAccess W2911451279 @default.
• W2911451279 hasPrimaryLocation W29114512791 @default.
• W2911451279 hasRelatedWork W161941179 @default.
• W2911451279 hasRelatedWork W2059903063 @default.
• W2911451279 hasRelatedWork W2060073496 @default.
• W2911451279 hasRelatedWork W2112042611 @default.
• W2911451279 hasRelatedWork W2431605961 @default.
• W2911451279 hasRelatedWork W2622466309 @default.
• W2911451279 hasRelatedWork W2983446470 @default.
• W2911451279 hasRelatedWork W3091588921 @default.
• W2911451279 hasRelatedWork W4235041219 @default.
• W2911451279 hasRelatedWork W4248876388 @default.
• W2911451279 hasVolume "132" @default.
• W2911451279 isParatext "false" @default.
• W2911451279 isRetracted "false" @default.
• W2911451279 magId "2911451279" @default.
• W2911451279 workType "article" @default.