Direct Conversion of Fibroblasts to Megakaryocyte Progenitors
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 differen...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471631275X |
| _version_ | 1818215645302489088 |
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| author | Julian Pulecio Oriol Alejo-Valle Sandra Capellera-Garcia Marianna Vitaloni Paula Rio Eva Mejía-Ramírez Ilaria Caserta Juan A. Bueren Johan Flygare Angel Raya |
| author_facet | Julian Pulecio Oriol Alejo-Valle Sandra Capellera-Garcia Marianna Vitaloni Paula Rio Eva Mejía-Ramírez Ilaria Caserta Juan A. Bueren Johan Flygare Angel Raya |
| author_sort | Julian Pulecio |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T06:39:22Z |
| format | Article |
| id | doaj.art-c1bd0d0a0a724be3802e79b05af1ecf5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T06:39:22Z |
| publishDate | 2016-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c1bd0d0a0a724be3802e79b05af1ecf52022-12-22T00:34:24ZengElsevierCell Reports2211-12472016-10-0117367168310.1016/j.celrep.2016.09.036Direct Conversion of Fibroblasts to Megakaryocyte ProgenitorsJulian Pulecio0Oriol Alejo-Valle1Sandra Capellera-Garcia2Marianna Vitaloni3Paula Rio4Eva Mejía-Ramírez5Ilaria Caserta6Juan A. Bueren7Johan Flygare8Angel Raya9Center of Regenerative Medicine in Barcelona (CMRB), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, SpainCenter of Regenerative Medicine in Barcelona (CMRB), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, SpainDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 22184 Lund, SwedenCenter of Regenerative Medicine in Barcelona (CMRB), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, SpainDivision 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, SpainCenter of Regenerative Medicine in Barcelona (CMRB), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, SpainCenter of Regenerative Medicine in Barcelona (CMRB), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, SpainDivision 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, SpainDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Centre, Lund University, 22184 Lund, SwedenCenter of Regenerative Medicine in Barcelona (CMRB), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, SpainCurrent 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.http://www.sciencedirect.com/science/article/pii/S221112471631275Xtransdifferentiationlineage conversionFanconi anemiathrombocytopeniaplatelets |
| spellingShingle | Julian Pulecio Oriol Alejo-Valle Sandra Capellera-Garcia Marianna Vitaloni Paula Rio Eva Mejía-Ramírez Ilaria Caserta Juan A. Bueren Johan Flygare Angel Raya Direct Conversion of Fibroblasts to Megakaryocyte Progenitors Cell Reports transdifferentiation lineage conversion Fanconi anemia thrombocytopenia platelets |
| title | Direct Conversion of Fibroblasts to Megakaryocyte Progenitors |
| title_full | Direct Conversion of Fibroblasts to Megakaryocyte Progenitors |
| title_fullStr | Direct Conversion of Fibroblasts to Megakaryocyte Progenitors |
| title_full_unstemmed | Direct Conversion of Fibroblasts to Megakaryocyte Progenitors |
| title_short | Direct Conversion of Fibroblasts to Megakaryocyte Progenitors |
| title_sort | direct conversion of fibroblasts to megakaryocyte progenitors |
| topic | transdifferentiation lineage conversion Fanconi anemia thrombocytopenia platelets |
| url | http://www.sciencedirect.com/science/article/pii/S221112471631275X |
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