CDK8/19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes.

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  • Additional Information
    • Source:
      Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0372544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2141 (Electronic) Linking ISSN: 00071048 NLM ISO Abbreviation: Br J Haematol Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Wiley-Blackwell
      Original Publication: Oxford : Blackwell Scientific Publications
    • Subject Terms:
      Megakaryocytes*/metabolism ; Fetal Blood*/cytology ; Mitosis* ; Cyclin-Dependent Kinase 8*/antagonists & inhibitors ; Cyclin-Dependent Kinases*/antagonists & inhibitors; Humans ; Ploidies ; Protein Kinase Inhibitors/pharmacology ; Cell Proliferation ; Cells, Cultured
    • Abstract:
      Neonatal and adult megakaryocytes differ in proliferative capacity and ploidy levels, and neonatal and adult platelets differ in function, gene expression, and protein content. The mechanisms underlying these differences are incompletely understood. CDK8 and CDK19 are transcriptional kinases part of the CDK-mediator complex, which regulates gene transcription in a cell-specific manner. We discovered that cortistatin A, a potent highly selective inhibitor of CDK8/CDK19, significantly reduced cell expansion and increased ploidy in cord blood-derived megakaryocytes. These phenotypic changes were associated with gene expression changes that partially overlapped developmentally regulated genes. These findings might have relevance for the management of developmental megakaryocyte disorders.
      (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
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    • Grant Information:
      HL046925 United States HL NHLBI NIH HHS; K99 HL156052 United States HL NHLBI NIH HHS; R01 HL069990 United States HL NHLBI NIH HHS; HL156052 United States HL NHLBI NIH HHS; HL69990 United States HL NHLBI NIH HHS; P01 HL046925 United States HL NHLBI NIH HHS
    • Contributed Indexing:
      Keywords: cord blood; megakaryocytes; neonatal haematology; transcription
    • Accession Number:
      EC 2.7.11.22 (Cyclin-Dependent Kinase 8)
      EC 2.7.11.22 (Cyclin-Dependent Kinases)
      EC 2.7.11.22 (CDK19 protein, human)
      EC 2.7.11.22 (CDK8 protein, human)
      0 (Protein Kinase Inhibitors)
    • Publication Date:
      Date Created: 20241016 Date Completed: 20241212 Latest Revision: 20241214
    • Publication Date:
      20241214
    • Accession Number:
      PMC11637730
    • Accession Number:
      10.1111/bjh.19836
    • Accession Number:
      39413769