ArticleBlood2014
Defective endomitosis during megakaryopoiesis leads to thrombocytopenia in Fanca-/- mice.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Inflammatory pathways and the bone marrow microenvironment in inherited bone marrow failure syndromes.Stem cells (Dayton, Ohio) · 2025Review
- Identifying an AML Prognostic Model Using 10 Marker Genes from Single-Cell Transcriptome and Bulk Transcriptome Analysis.Biochemical genetics · 2024Article
- Fanca deficiency is associated with alterations in osteoclastogenesis that are rescued by TNFα.Cell & bioscience · 2023Article
- SIK2 kinase synthetic lethality is driven by spindle assembly defects in FANCA-deficient cells.Molecular oncology · 2022Article
- The Y14-p53 regulatory circuit in megakaryocyte differentiation and thrombocytopenia.iScience · 2021Article
- Polyploid cardiomyocytes: implications for heart regeneration.Development (Cambridge, England) · 2021Article
- FANCD2 modulates the mitochondrial stress response to prevent common fragile site instability.Communications biology · 2021Article
- Clonal hematopoietic mutations linked to platelet traits and the risk of thrombosis or bleeding.Haematologica · 2020Review
- The FANC/BRCA Pathway Releases Replication Blockades by Eliminating DNA Interstrand Cross-Links.Genes · 2020Review
- Microphthalmia transcription factor expression contributes to bone marrow failure in Fanconi anemia.The Journal of clinical investigation · 2020Article
- Fanconi anaemia and cancer: an intricate relationship.Nature reviews. Cancer · 2018Review
- Rescue from replication stress during mitosis.Cell cycle (Georgetown, Tex.) · 2017Review
- Estrogen promotes megakaryocyte polyploidization via estrogen receptor beta-mediated transcription of GATA1.Leukemia · 2017Article
- Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fanconi anemia (FA) is an inherited chromosomal instability syndrome that is characterized by progressive bone marrow failure. One of the main causes of morbidity and mortality in FA is a bleeding tendency, resulting from low platelet counts. Platelets are the final products of megakaryocyte (MK) maturation. Here, we describe a previously unappreciated role of Fanconi anemia group A protein (Fanca) during the endomitotic process of MK differentiation. Fanca deficiency leads to the accumulation of MKs with low nuclear ploidy and to decreased platelet production. We show, for the first time, that Fanca(-/-) mice are characterized by limited number and proliferative capacity of MK progenitors. Defective megakaryopoiesis of Fanca(-/-) cells is associated with the formation of nucleoplasmic bridges and increased chromosomal instability, indicating that inaccurate endoreplication and karyokinesis occur during MK polyploidization. Sustained DNA damage forces Fanca(-/-) MKs to enter a senescence-like state. Furthermore, inhibition of the Rho-associated kinase, a regulator of cytokinesis, improves the polyploidization of Fanca(-/-) MKs but greatly increases their genomic instability and diminishes their differentiation potential, supporting the notion that accumulation of DNA damage through endomitotic cycles affects MK maturation. Our study indicates that Fanca expression during endomitosis is crucial for normal megakaryopoiesis and platelet production.
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