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Nature：一种miRNA控制干细胞自我更新
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+ e z; ^7 `3 v胚胎干细胞的分化既需要对自我更新进行抑制，又需要对一个特定的分化通道进行激发。被称为微RNA（miRNA）的小型非编码RNA作为支配细胞命运的重要物质正在被人们所认识。
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5 v5 |2 z/ t9 F# o# I5 @# j现在研究发现，一种名为“let-7”的著名miRNA负责抑制胚胎干细胞中的自我更新程序。这种抑制可以被一组“胚胎干细胞调控型miRNA”（称之为ESCC miRNA，它们调控细胞周期）逆转，说明“let-7”和ESCC miRNA之间的互动提供一个能够支配细胞命运的机制。) I. h% j! a: v- X
+ ~9 ?3 o8 \1 \& G* [" ?$ C/ J4 ]原始出处：: R6 h5 ]% K) k& W# j) g
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Nature 463, 621-626 (4 February 2010) | doi:10.1038/nature08725
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Opposing microRNA families regulate self-renewal in mouse embryonic stem cells( j' x0 u3 b6 s1 E! @
! q8 j5 ^$ a; d H1 f6 [) kCollin Melton1,2, Robert L. Judson1,2 & Robert Blelloch1,2
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1 The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Program in Biomedical Sciences,
) U: B5 {6 T3 {* M! x2 Department of Urology, University of California San Francisco, San Francisco, California 94143, USA! G% P. _1 c4 `6 X0 N9 H
% ]% E1 i2 f' ?. ]" k6 xWhen embryonic stem cells (ESCs) differentiate, they must both silence the ESC self-renewal program and activate new tissue-specific programs. In the absence of DGCR8 (Dgcr8 -/-), a protein required for microRNA (miRNA) biogenesis, mouse ESCs are unable to silence self-renewal. Here we show that the introduction of let-7 miRNAs—a family of miRNAs highly expressed in somatic cells—can suppress self-renewal in Dgcr8 -/- but not wild-type ESCs. Introduction of ESC cell cycle regulating (ESCC) miRNAs into the Dgcr8 -/- ESCs blocks the capacity of let-7 to suppress self-renewal. Profiling and bioinformatic analyses show that let-7 inhibits whereas ESCC miRNAs indirectly activate numerous self-renewal genes. Furthermore, inhibition of the let-7 family promotes de-differentiation of somatic cells to induced pluripotent stem cells. Together, these findings show how the ESCC and let-7 miRNAs act through common pathways to alternatively stabilize the self-renewing versus differentiated cell fates. |
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发表于 2010-6-26 21:57
