Abstract
Current sources of platelets for transfusion are insufficient and associated with risk of alloimmunization and blood-borne infection. These limitations could be addressed by the generation of autologous megakaryocytes (MKs) derived invitro from somatic cells with the ability to engraft and differentiate invivo. Here, we show that overexpression of a defined set of six transcription factors efficiently converts mouse and human fibroblasts into MK-like progenitors. The transdifferentiated cells are CD41+, display polylobulated nuclei, have ploidies higher than 4N, form MK colonies, and give rise to platelets invitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation invivo. Similar results are obtained using disease-corrected fibroblasts from Fanconi anemia patients. Our results combined demonstrate that functional MK progenitors with clinical potential can be obtained invitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells.
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