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Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

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 (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
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Reports
volume
17
issue
3
pages
13 pages
publisher
Cell Press
external identifiers
  • 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
2017-11-12 04:25:41
@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},
  volume       = {17},
  year         = {2016},
}