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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;
! o1 _( D! ~" H# W ~& HAccepted 20 October 2010; Published online 7 November 2010
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Direct conversion of human fibroblasts to multilineage blood progenitors
2 c7 g4 B: G+ FEva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2,( G9 M3 h9 m8 r) }
Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2 * u1 b |7 y$ i
1 w$ j0 \( ?8 J3 _1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 * f9 k7 W( }- _% e& k4 A
2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
. I- b/ s9 @( i" l7 I. yCorrespondence to: Mickie Bhatia1,2 Email: mbhatia@mcmaster.ca
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! h4 a7 y7 k3 L3 W, n3 \$ nAbstract : As is the case for embryo-derived stem cells, application of reprogrammed human induced pluripotent stem cells is limited by our understanding 8 u4 \7 ?% y5 H/ Y4 p, D/ @
of lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal ) u, _* }8 w9 D5 f+ s+ B# s* j
fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together
. n) \) L: N1 ?! O% V/ ^4 a* l1 F( N9 pwith specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise
1 W" T4 Q. f0 `# s' d2 Q0 L, D$ vto granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic
2 G) _ Y1 z# e; @programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent * e4 e. b; x; D' ^; o( W' l
stem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an
" o; c& {2 i( e3 ?0 oalternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human ! \, U1 }1 A1 D4 D' J( r8 D& J T
pluripotent stem cells. |
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