ArticleThe Journal of clinical investigation2022
Relieving DYRK1A repression of MKL1 confers an adult-like phenotype to human infantile megakaryocytes.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 12 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Laboratory Assessment and Clinical Outlook forAnnals of laboratory medicine · 2026Review
- The Kifc3 Motor Protein Controls Centrosomal Factor Cep192 in Ontogenic Coordination of Megakaryocyte Development.bioRxiv : the preprint server for biology · 2026Article
- Megakaryocyte centrosomal and Golgi structural perturbations in patients with primary myelofibrosis and withLeukemia & lymphoma · 2025Article
- DYRK1A in blood and immune function: implications in leukemia, inflammatory disorders, infection and Down syndrome.Frontiers in cell and developmental biology · 2025Review
- Downregulation of ABLIM3 confers to the metastasis of neuroblastoma via regulating the cell adhesion molecules pathway.Computational and structural biotechnology journal · 2024Article
- Novel Thiazole-Fused [4,5-Pharmaceuticals (Basel, Switzerland) · 2024Article
- Nuclear F-actin assembly on damaged chromatin is regulated by DYRK1A and Spir1 phosphorylation.Nucleic acids research · 2024Article
- Baffled-flow culture system enables the mass production of megakaryocytes from human embryonic stem cells by enhancing mitochondrial function.Cell proliferation · 2023Article
- Synergistic roles of DYRK1A and GATA1 in trisomy 21 megakaryopoiesis.JCI insight · 2023Article
- Over-expression of Dyrk1A affects bleeding by modulating plasma fibronectin and fibrinogen level in mice.Journal of cellular and molecular medicine · 2023Article
- Review
- Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes.Journal of Zhejiang University. Science. BReview
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Authors and funding
21 authors at 7 institutions in 4 countries.
Funding
Abstract
Infantile (fetal and neonatal) megakaryocytes (Mks) have a distinct phenotype consisting of hyperproliferation, limited morphogenesis, and low platelet production capacity. These properties contribute to clinical problems that include thrombocytopenia in neonates, delayed platelet engraftment in recipients of cord blood stem cell transplants, and inefficient ex vivo platelet production from pluripotent stem cell-derived Mks. The infantile phenotype results from deficiency of the actin-regulated coactivator, MKL1, which programs cytoskeletal changes driving morphogenesis. As a strategy to complement this molecular defect, we screened pathways with the potential to affect MKL1 function and found that DYRK1A inhibition dramatically enhanced Mk morphogenesis in vitro and in vivo. Dyrk1 inhibitors rescued enlargement, polyploidization, and thrombopoiesis in human neonatal Mks. Mks derived from induced pluripotent stem cells responded in a similar manner. Progenitors undergoing Dyrk1 inhibition demonstrated filamentous actin assembly, MKL1 nuclear translocation, and modulation of MKL1 target genes. Loss-of-function studies confirmed MKL1 involvement in this morphogenetic pathway. Expression of Ablim2, a stabilizer of filamentous actin, increased with Dyrk1 inhibition, and Ablim2 knockdown abrogated the actin, MKL1, and morphogenetic responses to Dyrk1 inhibition. These results delineate a pharmacologically tractable morphogenetic pathway whose manipulation may alleviate clinical problems associated with the limited thrombopoietic capacity of infantile Mks.
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