Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 11, Issue 4, Pages 593-604Publisher
WILEY-BLACKWELL
DOI: 10.1111/jth.12131
Keywords
megakaryocyte; platelet formation; thrombocytopenia; transcription factor
Categories
Funding
- Marie Curie Intra-European Fellow [237296]
- National Institute for Health Research [RP-PG-0310-1002]
- British Heart Foundation [FS/09/039]
- National Institutes of Health Research (NIHR) [RP-PG-0310-1002] Funding Source: National Institutes of Health Research (NIHR)
- British Heart Foundation [FS/09/039/27788] Funding Source: researchfish
- National Institute for Health Research [RP-PG-0310-1002] Funding Source: researchfish
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Cell type-specific transcription factors regulate the repertoire of genes expressed in a cell and thereby determine its phenotype. The differentiation of megakaryocytes, the platelet progenitors, from hematopoietic stem cells is a well-known process that can be mimicked in culture. However, the efficient formation of platelets in culture remains a challenge. Platelet formation is a complicated process including megakaryocyte maturation, platelet assembly and platelet shedding. We hypothesize that a better understanding of the transcriptional regulation of this process will allow us to influence it such that sufficient numbers of platelets can be produced for clinical applications. After an introduction to gene regulation and platelet formation, this review summarizes the current knowledge of the regulation of platelet formation by the transcription factors EVI1, GATA1, FLI1, NFE2, RUNX1, SRF and its co-factor MKL1, and TAL1. Also covered is how some platelet disorders including myeloproliferative neoplasms, result from disturbances of the transcriptional regulation. These disorders give us invaluable insights into the crucial role these transcription factors play in platelet formation. Finally, there is discussion of how a better understanding of these processes will be needed to allow for efficient production of platelets in vitro.
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