Platelet generation from circulating megakaryocytes is triggered in the lung vasculature
Zhao, X.; Alibhai, D.; Walsh, T. G.; Tarassova, N.; Birol, S. Z.; Williams, C. M.; Neil, C. R.; Aitken, E. W.; Waller, A. K.; Ballester-Beltran, J.; Gunning, P. W.; Hardeman, E. C.; Agbani, E. O.; Hers, I.; Ghevaert, C.; Poole, A. W.
Show abstract
Platelets, small hemostatic blood cells, are derived from megakaryocytes, although the generation process is not clear. Only small numbers of platelets have been produced in systems outside the body, where bone marrow and lung are proposed as sites of platelet generation. Here we show that perfusion of megakaryocytes ex vivo through the mouse lung vasculature generates very large numbers of platelets, up to 3,000 per megakaryocyte. Despite their large size, megakaryocytes were able repeatedly to passage through the lung vasculature, leading to enucleation and fragmentation to generate platelets intravascularly. Using the ex vivo lung and a novel in vitro microfluidic chamber we determined the contributions of oxygenation, ventilation and endothelial cell health to platelet generation, and showed a critical role for the actin regulator TPM4. One-Sentence SummaryMegakaryocytes form platelets intravascularly in the lung, dependent upon oxygenation, endothelium and megakaryocyte TPM4
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Circulating BMP9 protects the pulmonary endothelium during inflammation-induced lung injury in mice 93%
- Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy 93%
- Endogenous Retroviral Elements Generate Pathologic Neutrophils and Elastase Rich Exosomes in Pulmonary Arterial Hypertension 92%
Similar papers in this journal
- Single-cell and Spatial Transcriptomics Identified Fatty Acid-binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension 92%
- Synaptotagmin-like protein 2a regulates lumen formation via Weibel-Palade body apical secretion of angiopoietin-2 during angiogenesis 92%
- Cytokine-Mediated Degradation of the Transcription Factor ERG Impacts the Pulmonary Vascular Response to Systemic Inflammatory Challenge 92%
Similar papers in this journal
- Single Cell RNA-seq reveals ectopic and aberrant lung resident cell populations in Idiopathic Pulmonary Fibrosis 92%
- Xenogeneic Skin Transplantation Promotes Angiogenesis and Tissue Regeneration Through Vitamin D-Activated Trem2+ Macrophages 92%
- Reduced platelet forces underlie impaired hemostasis in mouse models of MYH9-related disease 92%
Similar papers in this journal
- Capillary regression leads to sustained local hypoperfusion by inducing constriction of upstream transitional vessels 93%
- Intussusceptive angiogenesis-on-a-chip: Evidence for transluminal vascular bridging by endothelial delamination 92%
- NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin de-condensation and nuclear envelope rupture 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.