Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

Cell Reports

Ilaria Caserta¹  Eva Mejía-Ramírez¹  Angel Raya¹  Julian Pulecio¹  Marianna Vitaloni¹  Oriol Alejo-Valle¹  Johan Flygare²  Sandra Capellera-Garcia²  Juan A. Bueren³  Paula Rio³ 

[1] Center of Regenerative Medicine in Barcelona (CMRB), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, Spain;Department of Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 22184 Lund, Sweden;Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIEMAT/CIBERER-ISCIII), 28040 Madrid, Spain;

关键词: transdifferentiation;    lineage conversion;    Fanconi anemia;    thrombocytopenia;    platelets;   

DOI  :  10.1016/j.celrep.2016.09.036

来源: DOAJ

【 摘 要 】

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 in vitro from somatic cells with the ability to engraft and differentiate in vivo. 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 in vitro. Moreover, transplantation of MK-like murine progenitor cells into NSG mice results in successful engraftment and further maturation in vivo. 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 in vitro, circumventing the use of hematopoietic progenitors or pluripotent stem cells.

【 授权许可】

Unknown