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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;
% \ Z( |2 R2 fAccepted 20 October 2010; Published online 7 November 2010
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Direct conversion of human fibroblasts to multilineage blood progenitors
( g. ]0 j m: q2 F4 H: Q3 u8 UEva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2,; ~0 ~4 w* m; e1 |5 [
Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2
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2 B7 j* K2 @: B( u2 ]' @1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
5 D. @% U/ m2 [$ c y# I# x& @7 b2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
" s! z5 c5 ]2 l: d6 YCorrespondence to: Mickie Bhatia1,2 Email: mbhatia@mcmaster.ca
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1 Q4 B- A7 S: c# sAbstract : As is the case for embryo-derived stem cells, application of reprogrammed human induced pluripotent stem cells is limited by our understanding
2 c4 J) P% v5 s3 \, O% d+ Pof lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal N4 K9 y% r" _; p5 n
fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together + }7 f4 c+ \4 w4 Q: C- S
with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise
6 m6 a5 g! v/ S8 c1 V* Z4 Q' xto granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic 9 o4 t3 B% e7 K. V+ K' n3 z
programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent - r# } x- B2 ^8 c7 \& k' q1 U
stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an
* b. c% c" w% q& F9 halternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human 9 \5 F% n, _3 }, }# F+ q' b
pluripotent stem cells. |
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