Direct Conversion of Fibroblasts to Megakaryocyte Progenitors
(2016) In Cell Reports 17(3). p.671-683- 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 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... (More)
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.
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- author
- Pulecio, Julian ; Alejo-Valle, Oriol ; Capellera-Garcia, Sandra LU ; Vitaloni, Marianna ; Rio, Paula ; Mejía-Ramírez, Eva ; Caserta, Ilaria ; Bueren, Juan A ; Flygare, Johan LU and Raya, Angel
- organization
- publishing date
- 2016-10-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Reports
- volume
- 17
- issue
- 3
- pages
- 13 pages
- publisher
- Cell Press
- external identifiers
-
- pmid:27732845
- scopus:84992186826
- wos:000385852300007
- ISSN
- 2211-1247
- DOI
- 10.1016/j.celrep.2016.09.036
- language
- English
- LU publication?
- yes
- id
- a17c9f34-03d3-467a-8d4f-7efa004db946
- date added to LUP
- 2016-11-01 15:00:56
- date last changed
- 2024-09-22 00:56:56
@article{a17c9f34-03d3-467a-8d4f-7efa004db946, abstract = {{<p>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.</p>}}, author = {{Pulecio, Julian and Alejo-Valle, Oriol and Capellera-Garcia, Sandra and Vitaloni, Marianna and Rio, Paula and Mejía-Ramírez, Eva and Caserta, Ilaria and Bueren, Juan A and Flygare, Johan and Raya, Angel}}, issn = {{2211-1247}}, language = {{eng}}, month = {{10}}, number = {{3}}, pages = {{671--683}}, publisher = {{Cell Press}}, series = {{Cell Reports}}, title = {{Direct Conversion of Fibroblasts to Megakaryocyte Progenitors}}, url = {{http://dx.doi.org/10.1016/j.celrep.2016.09.036}}, doi = {{10.1016/j.celrep.2016.09.036}}, volume = {{17}}, year = {{2016}}, }