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Reprogramming fibroblasts into induced pluripotent stem cells with Bmi1
) Z/ @: W9 x' ]) _' m. f7 Y Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4,
+ @) l A. J) o6 o5 r' S( BSox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4
. V/ l7 I, w' ralone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1
6 d, d5 p% J8 o" x0 mleads to the transdifferentiation of mouse fibroblasts into NSC-like cells, and, in combination with Oct4, can replace % V2 L& o. z4 x- v
Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedge-
/ k2 U7 o8 I3 f3 e) |+ @hog signaling (by Shh, purmorphamine, or oxysterol) compensates for the effects of Bmi1, and, in combination with 0 @" q, k$ _ f. [& |/ l
Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One- and two-factor iPS cells are similar to , t: `* x$ {) `3 t6 b* Q* H( a$ e/ M
mouse embryonic stem cells in their global gene expression profile, epigenetic status, and in vitro and in vivo differ-
: V( d, ]3 t7 y* L% j0 }entiation into all three germ layers, as well as teratoma formation and germline transmission in vivo. These data sup-
U o3 l: G2 e9 t5 b: bport that converting fibroblasts with Bmi1 or activation of the sonic hedgehog pathway to an intermediate cell type 3 Z$ ] y4 T1 k# H
that expresses Sox2, Klf4, and N-Myc allows iPS generation via the addition of Oct4) Y$ S$ C( X9 h* G/ |
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Bmi1 重编程成纤维细胞为诱导多能干细胞4 C, n+ W0 ?. C: Z
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。
9 V. j5 w3 R% u9 r! w4 z0 V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.
$ Z. K! S; {2 U! A+ f3 [) L 有些地方翻的不准,仅供参考哈 |
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