胚胎干細胞的分化既需要對自我更新進行抑制,,又需要對一個特定的分化通道進行激發(fā),。被稱為微RNA(miRNA)的小型非編碼RNA作為支配細胞命運的重要物質(zhì)正在被人們所認識。
現(xiàn)在研究發(fā)現(xiàn),,一種名為“let-7”的著名miRNA負責(zé)抑制胚胎干細胞中的自我更新程序,。這種抑制可以被一組“胚胎干細胞調(diào)控型miRNA”(稱之為ESCC miRNA,它們調(diào)控細胞周期)逆轉(zhuǎn),,說明“let-7”和ESCC miRNA之間的互動提供一個能夠支配細胞命運的機制,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 463, 621-626 (4 February 2010) | doi:10.1038/nature08725
Opposing microRNA families regulate self-renewal in mouse embryonic stem cells
Collin Melton1,2, Robert L. Judson1,2 & Robert Blelloch1,2
1 The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Program in Biomedical Sciences,
2 Department of Urology, University of California San Francisco, San Francisco, California 94143, USA
When 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.