title: Transdifferentiation of erythroblasts to megakaryocytes using FLI1 and ERG transcription factors.
abstract: 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.
authors.forename: Darin
authors.initials: D
authors.lastname: Siripin
authors.forename: Pakpoom
authors.initials: P
authors.lastname: Kheolamai
authors.forename: Yaowalak
authors.initials: Y
authors.lastname: U-Pratya
authors.forename: Aungkura
authors.initials: A
authors.lastname: Supokawej
authors.forename: Methichit
authors.initials: M
authors.lastname: Wattanapanitch
authors.forename: Nuttha
authors.initials: N
authors.lastname: Klincumhom
authors.forename: Chuti
authors.initials: C
authors.lastname: Laowtammathron
authors.affiliation: Prof. Surapol Issaragrisil, Division of Hematology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand, Tel.: +662 419 4448 50, Fax: +662 411 2012, E-mail: surapolsi@gmail.com.
authors.forename: Surapol
authors.initials: S
authors.lastname: Issaragrisil
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001777:Blood Coagulation; D049109:Cell Proliferation; D048430:Cell Shape; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D004900:Erythroblasts / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism*; D010641:Phenotype; D010974:Platelet Aggregation; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism*; D053628:Receptors, Thrombopoietin / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C072312:ERG protein, human; C078433:FLI1 protein, human; D040201:Platelet Membrane Glycoprotein IIb; D051789:Proto-Oncogene Protein c-fli-1; D053628:Receptors, Thrombopoietin; C578986:TUBB1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014404:Tubulin; C082218:MPL protein, human
keywords: Transdifferentiation; erythroblast; megakaryocyte; platelet; transcription factors