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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; ' Y: `3 n) C& m8 A0 ~
Accepted 20 October 2010; Published online 7 November 2010 # t5 F3 \$ O' f( U: g2 m; [
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Direct conversion of human fibroblasts to multilineage blood progenitors 2 T' E$ Q6 v( u, M' W
Eva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2," y$ `0 ^& L! o) s, V
Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2 # s+ v% {3 ^* Y6 O a& k9 O
% g& j# Z& b! s8 |/ s# ^1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
+ u+ a z+ C8 }8 }7 H& z2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 ( ^1 D4 J$ w1 I. Q3 ~) ^" J
Correspondence to: Mickie Bhatia1,2 Email: mbhatia@mcmaster.ca X# j2 N& n- o* E* Z, B
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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
# R" b, C) e* D' S8 P; g' @of lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal ; s0 d5 |1 y0 g& o9 r8 i
fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together 2 t) E! Q$ ]7 A$ q. Y
with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise
. o" x$ F8 Y8 bto granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic 8 {+ _# a* } O
programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent # K% U. f; N6 j& v
stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an # e$ k4 N8 m- q8 g, w9 C
alternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human & B- P1 |) C) T1 ~
pluripotent stem cells. |
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