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发表于 2010-11-30 20:33:22
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Nature 468, 521-526 (25 November 2010) | doi:10.1038/nature09591; Received 17 August 2010;
5 ~' P7 w3 e# DAccepted 20 October 2010; Published online 7 November 2010 , C9 p+ t- r3 t0 V; L
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) S9 T4 m3 m3 H# K0 hDirect conversion of human fibroblasts to multilineage blood progenitors 7 l0 e! f& g8 Z
Eva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2,) t4 w, ]: A7 Z2 ^7 S
Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2 / k4 N* D5 T4 S4 C9 ~. }
7 E3 v1 E7 s; {1 B; }2 y6 [1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 2 w- [; ^) V/ N/ Q! n
2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 ) E/ `* U- ~. b
Correspondence to: Mickie Bhatia1,2 Email: mbhatia@mcmaster.ca
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Abstract : As is the case for embryo-derived stem cells, application of reprogrammed human induced pluripotent stem cells is limited by our understanding
- k% \% I; a2 Y; |2 I S kof lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal
" i: p2 l3 [' e5 e# }! e N fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together 2 ~6 K+ B1 U! k0 ?* L; G
with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise
' B7 S6 F- n/ @. G7 G% k7 jto granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic 8 Y6 S! ?$ w; b4 ~
programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent ! O, i) `, { o% _
stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an
, \2 \. j6 b* H) i, Galternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human 1 v: r$ j) M" P* ~6 j/ ]
pluripotent stem cells. |
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