ArticleProceedings of the National Academy of Sciences of the United States of America2011
Myosin-II inhibition and soft 2D matrix maximize multinucleation and cellular projections typical of platelet-producing megakaryocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 86 citations in OpenAlex.
- MYH9: Structure, functions, and therapeutic implications in cancer and genetic disorders.Genes & diseases · 2026Review
- Machine learning-driven single-cell phenotyping in size-controlled microenvironmentsLab on a chip · 2026Article
- Optimizing the Method for Differentiation of Functional Platelets from Human Induced Pluripotent Stem Cells.Stem cell reviews and reports · 2026Article
- New insights into the generation and function of megakaryocytes in health and disease.Haematologica · 2025Review
- Large-scale control over collective cell migration using light-activated epidermal growth factor receptors.Cell systems · 2025Article
- Mechanical confinement prevents ectopic platelet release.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Newly identified roles for PIEZO1 mechanosensor in controlling normal megakaryocyte development and in primary myelofibrosis.American journal of hematology · 2024Article
- Exploring the nexus between MYH9 and tumors: novel insights and new therapeutic opportunities.Frontiers in cell and developmental biology · 2024Review
- Towards single cell encapsulation for precision biology and medicine.Advanced drug delivery reviews · 2023Review
- Matrix stiffness controls megakaryocyte adhesion, fibronectin fibrillogenesis, and proplatelet formation through Itgβ3.Blood advances · 2023Article
- Micropipette-based biomechanical nanotools on living cells.European biophysics journal : EBJ · 2022Review
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
- Cytoskeletal-based mechanisms differently regulateHaematologica · 2021Article
- Generation and manipulation of human iPSC-derived platelets.Cellular and molecular life sciences : CMLS · 2021Review
- Hydrogel Micropost Arrays with Single Post Tunability to Study Cell Volume and Mechanotransduction.Advanced biosystems · 2020Article
- Article
- Targeting Actomyosin Contractility Suppresses Malignant Phenotypes of Acute Myeloid Leukemia Cells.International journal of molecular sciences · 2020Article
- Review
- Using genome editing to engineer universal platelets.Emerging topics in life sciences · 2019Article
- Nuclear rupture at sites of high curvature compromises retention of DNA repair factors.The Journal of cell biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cell division, membrane rigidity, and strong adhesion to a rigid matrix are all promoted by myosin-II, and so multinucleated cells with distended membranes--typical of megakaryocytes (MKs)--seem predictable for low myosin activity in cells on soft matrices. Paradoxically, myosin mutations lead to defects in MKs and platelets. Here, reversible inhibition of myosin-II is sustained over several cell cycles to produce 3- to 10-fold increases in polyploid MK and a number of other cell types. Even brief inhibition generates highly distensible, proplatelet-like projections that fragment readily under shear, as seen in platelet generation from MKs in vivo. The effects are maximized with collagenous matrices that are soft and 2D, like the perivascular niches in marrow rather than 3D or rigid, like bone. Although multinucleation of other primary hematopoietic lineages helps to generalize a failure-to-fission mechanism, lineage-specific signaling with increased polyploidy proves possible and novel with phospho-regulation of myosin-II heavy chain. Label-free mass spectrometry quantitation of the MK proteome uses a unique proportional peak fingerprint (ProPF) analysis to also show upregulation of the cytoskeletal and adhesion machinery critical to platelet function. Myosin-inhibited MKs generate more platelets in vitro and also in vivo from the marrows of xenografted mice, while agonist stimulation activates platelet spreading and integrin αIIbβ3. Myosin-II thus seems a central, matrix-regulated node for MK-poiesis and platelet generation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.