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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; 8 ]0 o. N F; C, S
Accepted 20 October 2010; Published online 7 November 2010
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Direct conversion of human fibroblasts to multilineage blood progenitors
& R' o7 a; l2 nEva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2,: `4 r. P+ _2 S& d
Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2 . O Q3 Y# y5 R! C) |: P
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1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
9 c) Z. J5 L% k9 T* ^# D2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
8 k$ n2 A' I+ j. ~, H. [! LCorrespondence to: Mickie Bhatia1,2 Email: mbhatia@mcmaster.ca l( U) x, R# @0 U
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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
9 V4 ]- X p2 m/ sof lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal + ~7 s* D# f+ H- y4 t
fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together
/ n, h7 q9 j& _2 }" |" ywith specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise
+ k/ T1 y0 \& }- D9 C0 t3 M( _to granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic , ? X5 J5 b* g! t5 r, \- {3 G
programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent / ]$ s5 r v! r/ m
stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an : ]( X# y, }0 v. D/ u6 C
alternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human
, s. o( \- p& w0 v9 qpluripotent stem cells. |
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