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Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1 2 E2 t2 h- f% G
Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, 7 G# ]! u+ K6 ], j, p& V
Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 0 _2 W3 W$ b; o+ C& S, I* b
alone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1 - ]# |9 N3 F; c) j! n- _
leads to the transdifferentiation of mouse fibroblasts into NSC-like cells, and, in combination with Oct4, can replace " W' F0 ]/ ^9 e; L' P
Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedge-; E. z9 _) r" P/ p* i2 W
hog signaling (by Shh, purmorphamine, or oxysterol) compensates for the effects of Bmi1, and, in combination with 7 H& f- t& V! E
Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One- and two-factor iPS cells are similar to . L5 `6 Y9 h U! V5 i6 v* q
mouse embryonic stem cells in their global gene expression profile, epigenetic status, and in vitro and in vivo differ-
% h. M% f( s+ w$ v# B% x# ]entiation into all three germ layers, as well as teratoma formation and germline transmission in vivo. These data sup-
* s+ @1 G8 i' F4 bport that converting fibroblasts with Bmi1 or activation of the sonic hedgehog pathway to an intermediate cell type
5 S) O& c6 v/ l& v: A6 R6 Hthat expresses Sox2, Klf4, and N-Myc allows iPS generation via the addition of Oct4
+ ~7 m" u* | P/ i4 K0 {; c0 y5 j" F& h& e) P8 ]9 O5 I
Bmi1 重编程成纤维细胞为诱导多能干细胞
. R) h( O! |# p; F# y' D9 l体细胞通过使用转录因子Oct4, Sox2, and Klf4,c-Myc能重编程为iPS。最近表明:Sox2加上Oct4也能重编程成纤维,oct4单独也能重编程小鼠和人的神经干细胞为iPS。
7 a( m* E2 G ^1 v" \9 @' o本文报道了, Bmi1能导致小鼠成纤维转分化为 NSC-类似细胞。并且它能结合oct4替代Sox2, Klf4 and c-Myc重编程成纤维细胞为iPS。此外,shh信号的激活 (by Shh, purmorphamine, or oxysterol)能补偿Bmi1的作用,在联合oct4能重编程小鼠胚胎和成体成纤维细胞为iPS。单因子和双因子的iPS的全基因表达图谱、表观水平与小鼠的胚胎干相似,并且在体外和体内能分化成所有的三个胚层,在体内也能形成畸胎瘤和生殖嵴传递。这些数据主持了:通过Bmi1或shh信号通路激活能转化成纤维细胞为表达Sox2, Klf4, and N-Myc 的一种过渡态细胞类型,这种细胞类型在外加oct4能产生iPS.
& Q/ {% P5 m) m7 I; P4 ~ 有些地方翻的不准,仅供参考哈 |
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