Publication: Effect of YAP/TAZ on megakaryocyte differentiation and platelet production
2
Issued Date
2020-08-01
Resource Type
ISSN
15734935
01448463
01448463
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2-s2.0-85089787767
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Mahidol University
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SCOPUS
Bibliographic Citation
Bioscience Reports. Vol.40, No.8 (2020)
Suggested Citation
Chanchao Lorthongpanich, Nittaya Jiamvoraphong, Phatchanat Klaihmon, Usaneeporn Lueangamornnara, Yaowalak Upratya, Chuti Laowtammathron, Surapol Issaragrisil Effect of YAP/TAZ on megakaryocyte differentiation and platelet production. Bioscience Reports. Vol.40, No.8 (2020). doi:10.1042/BSR20201780 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/58975
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Title
Effect of YAP/TAZ on megakaryocyte differentiation and platelet production
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Abstract
© 2020 The Author(s). Platelet transfusion is required for life-threatening thrombocytopenic bleeding, and single donor platelet concentrate is the ideal transfusion product. However, due to the inadequate number of donors that can donate a large volume of platelets, in vitro platelets production could be an alternative. We developed an in vitro production system designed to increase the platelet production yield from cultured cells. Previously, we reported that depletion of a Hippo pathway core kinase (LATS1/2) inhibited platelet production from cultured megakaryocytes. In the present study, we further investigated the role of the Hippo pathway in megakaryocyte proliferation and platelet production by focusing on the role of its effector proteins (YAP and TAZ), which are down-stream targets of LATS1/2 kinase. We found that YAP plays an essential role in megakaryoblastic cell proliferation, maturation, and platelet production, while TAZ showed minor effect. Knockdown of YAP, either by genetic manipulation or pharmaceutical molecule, significantly increased caspase-3-mediated apoptosis in cultured megakaryocytes, and increased platelet production as opposed to overexpressing YAP. We, therefore, demonstrate a paradigm for the regulation of megakaryocyte development and platelet production via the Hippo signaling pathway, and suggest the potential use of an FDA-approved drug to induce higher platelet production in cultured cells.