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Thromb Haemost 2017; 117(01): 116-126
DOI: 10.1160/TH16-07-0564
Cellular Haemostasis and Platelets
Schattauer GmbH

The Hippo pathway regulates human megakaryocytic differentiation

Chanchao Lorthongpanich
1   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Nittaya Jiamvoraphong
1   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Kantpitchar Supraditaporn
1   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Phatchanat Klaihmon
1   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
2   Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Yaowalak U-pratya
1   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
3   Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Surapol Issaragrisil
1   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
3   Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
› Author Affiliations Financial support: This research project was funded by grants from Thailand Research Fund (grant no. RTA 488–0007) and the Commission on Higher Education (grant no. CHE-RES-RG-49). S. Issaragrisil is a senior research scholar of Thailand Research Fund.
Further Information

Publication History

Received: 22 July 2017

Accepted after major revision: 29 September 2017

Publication Date:
01 December 2017 (online)

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Summary

The Hippo pathway is involved in several biological processes in both flies and mammals. Recent studies have shown that the Hippo pathway regulates Drosophila’s haematopoiesis; however, understanding of its role in mammalian haematopoiesis is still limited. In flies, deletion of the Hippo component gene, Warts, affects crystal cell differentiation. We explored the role of the Hippo pathway in human haemato-poiesis focusing on megakaryopoiesis. To investigate the role of LATS1/2 (a mammalian homolog of Warts) in human megakaryo -blastic cell differentiation and platelet formation, megakaryoblastic cell (MEG-01) line was used as a model to gain insight into mechan-ism of the Hippo pathway in mammalian megakaryopoiesis. Effect of LATS1/2 on megakaryoblastic cell differentiation and platelet production were determined by functional changes. We found that depletion of LATS1/2 resulted in an increase of CD41+ megakaryocytes with impaired platelet biogenesis. Our study shows that the Hippo signalling pathway plays a crucial role in human megakaryoblastic cell differentiation and thrombopoiesis.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Hippo pathway - LATS1/2 - megakaryocyte - platelet - thrombopoiesis

 

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