Direct Conversion of Fibroblasts to Megakaryocyte Progenitors

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 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.

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Center of Regenerative Medicine in Barcelona
  • Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi
  • Cell- och molekylärbiologi
Originalspråkengelska
Sidor (från-till)671-683
Antal sidor13
TidskriftCell Reports
Volym17
Utgivningsnummer3
StatusPublished - 2016 okt 11
PublikationskategoriForskning
Peer review utfördJa

Relaterad forskningsoutput

Sandra Capellera Garcia, 2018, Lund: Lund University, Faculty of Medicine. 111 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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