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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;
4 V1 f; x5 i* I; r, k2 ?3 u/ }Accepted 20 October 2010; Published online 7 November 2010
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5 \* C# W8 H* A; @Direct conversion of human fibroblasts to multilineage blood progenitors ! f q1 J7 t; H: A
Eva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2,
" `: B* d1 l- W) U) B Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2 # b: W# n9 p) n# y2 G9 ]
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1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
+ c, K# ^. G; w3 I2 q2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 ( t/ g# N0 Z$ F6 c( o
Correspondence to: Mickie Bhatia1,2 Email: mbhatia@mcmaster.ca - x* N2 B) E; t. w
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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 - @# |7 c2 {1 a, W: @
of lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal , J7 b' s# ]2 E
fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together 6 f8 ]3 k% c0 F6 F
with specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise 3 p0 n) ?/ G" L6 @) ]% ^3 ]' q
to granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic
5 z5 y1 h6 K G7 h# O1 D, p0 j* gprograms are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent ) G. b+ n; Z% { O( X
stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an " R$ k* Y, E5 l' c* h z% k6 l
alternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human
$ B1 m4 w# g1 Q+ i& p8 Z* Zpluripotent stem cells. |
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