Thromb Haemost 2015; 114(03): 593-602
DOI: 10.1160/TH14-12-1090
Cellular Haemostasis and Platelets
Schattauer GmbH

Transdifferentiation of erythroblasts to megakaryocytes using FLI1 and ERG transcription factors

Darin Siripin
1   Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
5   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Pakpoom Kheolamai
2   Division of Cell Biology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
3   Center of Excellence in Stem Cell Research, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
5   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Yaowalak U-Pratya
4   Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
5   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Aungkura Supokawej
1   Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
,
Methichit Wattanapanitch
5   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Nuttha Klincumhom
5   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Chuti Laowtammathron
5   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
,
Surapol Issaragrisil
4   Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
5   Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
› Institutsangaben
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).
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Publikationsverlauf

Received: 30. Dezember 2014

Accepted after major revision: 11. April 2015

Publikationsdatum:
21. November 2017 (online)

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Summary

Platelet transfusion has been widely used to prevent and treat life-threatening thrombocytopenia; however, preparation of a unit of concentrated platelet for transfusion requires at least 4–6 units of whole blood. At present, a platelet unit from a single donor can be prepared using apheresis, but lack of donors is still a major problem. Several approaches to produce platelets from other sources, such as haematopoietic stem cells and pluripotent stem cells, have been attempted but the system is extremely complicated, time-consuming and expensive. We now report a novel and simpler technology to obtain platelets using transdifferentiation of human bone marrow erythroblasts to megakaryocytes with overexpression of the FLI1 and ERG genes. The obtained transdifferentiated erythroblasts (both from CD71+ and GPA+ erythroblast subpopulations) exhibit typical features of megakaryocytes including morphology, expression of specific genes (cMPL and TUBB1) and a marker protein (CD41). They also have the ability to generate megakaryocytic CFU in culture and produce functional platelets, which aggregate with normal human platelets to form a normal-looking clot. Overexpression of FLI1 and ERG genes is sufficient to transdifferentiate erythroblasts to megakaryocytes that can produce functional platelets.