ArticleHaematologica2016
Uncoupling of the Hippo and Rho pathways allows megakaryocytes to escape the tetraploid checkpoint.
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Temporal Lysophosphatidic Acid Supplementation Enhances Megakaryocyte Differentiation and Platelet Production From Human Hematopoietic Progenitors.Cell biology international · 2026Article
- Associations of genetic variants with gene expression factors reveal biological pathways underlying complex traits.American journal of human genetics · 2026Article
- Macrophage-Derived Type 1 IFN, Renal Tubular Epithelial Cell Polyploidization, and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2025Article
- The antagonistic relationship between apoptosis and polyploidy in development and cancer.Seminars in cell & developmental biology · 2024Review
- Role of YAP in hematopoietic differentiation and erythroid lineage specification of human-induced pluripotent stem cells.Stem cell research & therapy · 2023Article
- Emerging role of Hippo pathway in the regulation of hematopoiesis.BMB reports · 2023Review
- Whole-Genome Doubling as a source of cancer: how, when, where, and why?Frontiers in cell and developmental biology · 2023Review
- Article
- BMP2K dysregulation promotes abnormal megakaryopoiesis in acute megakaryoblastic leukemia.Cell & bioscience · 2020Article
- Cytokinesis defects and cancer.Nature reviews. Cancer · 2019Review
- p53 shades of Hippo.Cell death and differentiation · 2018Review
- Article
- The Hippo-p53 pathway in megakaryopoiesis.Haematologica · 2016Article
- Endomitosis: a new cell fate in the cell cycle leading to polyploidy in megakaryocytes and hepatocytes.Journal of Zhejiang University. Science. BReview
- Role of Rho-GTPases in megakaryopoiesis.Small GTPasesReview
- RGFP966 inactivation of the YAP pathway attenuates cardiac dysfunction induced by prolonged hypothermic preservation.Journal of Zhejiang University. Science. BArticle
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Megakaryocytes are naturally polyploid cells that increase their ploidy by endomitosis. However, very little is known regarding the mechanism by which they escape the tetraploid checkpoint to become polyploid. Recently, it has been shown that the tetraploid checkpoint was regulated by the Hippo-p53 pathway in response to a downregulation of Rho activity. We therefore analyzed the role of Hippo-p53 pathway in the regulation of human megakaryocyte polyploidy. Our results revealed that Hippo-p53 signaling pathway proteins are present and are functional in megakaryocytes. Although this pathway responds to the genotoxic stress agent etoposide, it is not activated in tetraploid or polyploid megakaryocytes. Furthermore, Hippo pathway was observed to be uncoupled from Rho activity. Additionally, polyploid megakaryocytes showed increased expression of YAP target genes when compared to diploid and tetraploid megakaryocytes. Although p53 knockdown increased both modal ploidy and proplatelet formation in megakaryocytes, YAP knockdown caused no significant change in ploidy while moderately affecting proplatelet formation. Interestingly, YAP knockdown reduced the mitochondrial mass in polyploid megakaryocytes and decreased expression of PGC1α, an important mitochondrial biogenesis regulator. Thus, the Hippo pathway is functional in megakaryocytes, but is not induced by tetraploidy. Additionally, YAP regulates the mitochondrial mass in polyploid megakaryocytes.
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