<scp>CDK8</scp> /19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes

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.

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Publication Details

Journal
British Journal of Haematology
Published
2024-10-16
DOI
https://doi.org/10.1111/bjh.19836
Citations
2
Primary Topic
Ovarian cancer diagnosis and treatment
Type
article
Field-Weighted Citation Impact
1.07

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article

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

Francisca Ferrer‐Marín, Lisa M. Rimsza, Christopher S. Thom, Matthew D. Shair et al.
2 citations
British Journal of Haematology
Ovarian cancer diagnosis and treatment
1.07
article

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

Francisca Ferrer‐Marín, Lisa M. Rimsza, Christopher S. Thom, Matthew D. Shair, Martha Sola‐Visner, Henry E. Pelish, Raúl Teruel‐Montoya, Zhijian Liu, I Niţulescu
article en
2 citations

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.

British Journal of HaematologyVol. 205(6)
Boston Children's Hospital (US), Salk Institute for Biological Studies (US), Children's Hospital of Philadelphia (US), Harvard University (US), University of Arizona (US), Centro Regional de Hemodonación (ES), Covalent Associates (United States) (US), University of Pennsylvania (US)
National Heart, Lung, and Blood Institute
Good health and well-being
Openalex Percentile: Top 20%
Ovarian cancer diagnosis and treatment
1.07
DOIOpen Access PDFOpenAlex
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<scp>CDK8</scp> /19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes — Francisca Ferrer‐Marín, Lisa M. Rimsza, et al. · British Journal of Haematology (2024) | TGRS Research Map | TGRS