|
2#
楼主 |
发表于 2010-11-30 20:33:22
|
只看该作者
Nature 468, 521-526 (25 November 2010) | doi:10.1038/nature09591; Received 17 August 2010;
1 I1 R4 l" ^9 [% { e- J3 E2 H9 gAccepted 20 October 2010; Published online 7 November 2010
) Q' ^8 b# t/ Z% z, \( n6 y) X+ _. e4 D9 I, S! M
0 d9 n9 P7 h- _5 [& L: k0 y$ b! K+ }Direct conversion of human fibroblasts to multilineage blood progenitors
; O: i, K7 z4 t" eEva Szabo1, Shravanti Rampalli1, Ruth M. Risueño1, Angelique Schnerch1,2, Ryan Mitchell1,2,, w7 @' D" T& {- O! _# d
Aline Fiebig-Comyn1, Marilyne Levadoux-Martin1 & Mickie Bhatia1,2 - }6 U7 D1 c2 i/ i& _! g
1 {, `* S8 B. h: ?1.Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
6 t4 s! N4 j) I4 h" e2.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5
+ P* E- S6 B& r- F y+ y8 L+ FCorrespondence to: Mickie Bhatia1,2 Email: mbhatia@mcmaster.ca / `4 ^4 J7 c8 W$ K. m: D
3 X0 D5 V& @- q' d) Z- N# E' L, H/ MAbstract : As is the case for embryo-derived stem cells, application of reprogrammed human induced pluripotent stem cells is limited by our understanding
4 G' T% q t0 {of lineage specification. Here we demonstrate the ability to generate progenitors and mature cells of the haematopoietic fate directly from human dermal - D) ?* l; C% v0 d( ^8 J0 _; U# o
fibroblasts without establishing pluripotency. Ectopic expression of OCT4 (also called POU5F1)-activated haematopoietic transcription factors, together
4 O# w6 m3 y- w3 {. r8 J6 C$ twith specific cytokine treatment, allowed generation of cells expressing the pan-leukocyte marker CD45. These unique fibroblast-derived cells gave rise
1 B' g' I5 W: q( C3 U; Ito granulocytic, monocytic, megakaryocytic and erythroid lineages, and demonstrated in vivo engraftment capacity. We note that adult haematopoietic ( ]6 Y$ }$ f% Q. w5 x1 t
programs are activated, consistent with bypassing the pluripotent state to generate blood fate: this is distinct from haematopoiesis involving pluripotent
4 L8 ~8 Q$ F7 B8 A" y3 jstem cells, where embryonic programs are activated. These findings demonstrate restoration of multipotency from human fibroblasts, and suggest an
8 w8 c4 l1 n6 N/ C* U6 Y) Lalternative approach to cellular reprogramming for autologous cell-replacement therapies that avoids complications associated with the use of human ) j0 N1 y. l& ~! D: P, H
pluripotent stem cells. |
|