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

Summary 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...

Full description

Saved in:
Bibliographic Details
Published in:British journal of haematology 2024-12, Vol.205 (6), p.2481-2486
Main Authors: Liu, Zhi‐Jian, Thom, Christopher, Nitulescu, Ioana I., Pelish, Henry E., Rimsza, Lisa M., Teruel‐Montoya, Raul, Ferrer‐Marin, Francisca, Shair, Matthew D., Sola‐Visner, Martha
Format: Article
Language:English
Subjects:
Blood levels
Cell Proliferation
Cells, Cultured
Cord blood
Cyclin-Dependent Kinase 8 - antagonists & inhibitors
Cyclin-Dependent Kinases - antagonists & inhibitors
Fetal Blood - cytology
Gene expression
Humans
Megakaryocytes
Megakaryocytes - metabolism
Mitosis
neonatal haematology
Neonates
Ploidies
Ploidy
Protein Kinase Inhibitors - pharmacology
Short Report
transcription
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary 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.
ISSN:0007-1048
1365-2141
1365-2141
DOI:10.1111/bjh.19836