ArticleJournal of thrombosis and haemostasis : JTH2022
Conditional CRISPR-mediated deletion of Lyn kinase enhances differentiation and function of iPSC-derived megakaryocytes.
Article in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Redox Regulation of Megakaryocyte Differentiation and Platelet Biogenesis.Antioxidants (Basel, Switzerland) · 2026Review
- Functional classification of platelet gene variants using CRISPR HDR in CD34American journal of human genetics · 2025Article
- The LAT Rheostat as a Regulator of Megakaryocyte Activation.Thrombosis and haemostasis · 2024Article
- Megakaryocyte-induced contraction of plasma clots: cellular mechanisms and structural mechanobiology.Blood · 2024Article
- MCL-1 Inhibitor S63845 Distinctively Affects Intramedullary and Extramedullary Hematopoiesis.Pharmaceutics · 2023Article
- Engineered cord blood megakaryocytes evade killing by allogeneic T-cells for refractory thrombocytopenia.Frontiers in immunology · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThrombocytopenia leading to life-threatening excessive bleeding can be treated by platelet transfusion. Currently, such treatments are totally dependent on donor-derived platelets. To support future applications in the use of in vitro-derived platelets, we sought to identify genes whose manipulation might improve the efficiency of megakaryocyte production and resulting hemostatic effectiveness. Disruption of Lyn kinase has previously been shown to improve cell survival, megakaryocyte ploidy and TPO-mediated activation in mice, but its role in human megakaryocytes and platelets has not been examined.
methodsTo analyze the role of Lyn at defined differentiation stages during human megakaryocyte differentiation, conditional Lyn-deficient cells were generated using CRISPR/Cas9 technology in iPS cells. The efficiency of Lyn-deficient megakaryocytes to differentiate and become activated in response to a range of platelet agonists was analyzed in iPSC-derived megakaryocytes.
resultsTemporally controlled deletion of Lyn improved the in vitro differentiation of hematopoietic progenitor cells into mature megakaryocytes, as measured by the rate and extent of appearance of CD41
conclusionsConditional deletion of Lyn kinase increases the hemostatic effectiveness of megakaryocytes and their progeny as well as improving their yield. Adoption of this system during generation of in vitro-derived platelets may contribute to both their efficiency of production and their ability to support hemostasis.
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