來自美國休斯頓大學(xué)(University of Houston)，貝勒醫(yī)學(xué)院(Baylor College of Medicine),，W. M. Keck Center for Interdisciplinary Bioscience Training(W. M. Keck交叉學(xué)科生物科學(xué)培訓(xùn)中心),，德克薩斯大學(xué)(University of Texas),，以及美國LC Sciences公司的研究人員共同發(fā)表了題為"Novel MicroRNA Candidates and miRNA-mRNA Pairs in Embryonic Stem (ES) Cells"的論文,。
研究人員通過微陣列芯片篩選出545條新的小RNAs，它們在胚胎干細胞中的含量顯著高于成年細胞,。結(jié)合表達譜信息和對miRNA靶標(biāo)的預(yù)測,，研究人員發(fā)現(xiàn)了一系列miRNA-mRNA pairs與ES細胞的多功能化(pluripotence)和分化(differentiation)密切相關(guān)，進一步研究揭示出miRNA在調(diào)控ES細胞的自我更新(self-renewal),、多功能化和分化的核心網(wǎng)絡(luò)中起著重要的作用,。（生物谷Bioon.com）
生物谷推薦原始出處：
PLoS ONE 3(7): e2548. doi:10.1371/journal.pone.0002548 , Gu P, Reid JG, Gao X, Shaw CA, Creighton C, et al.
Novel MicroRNA Candidates and miRNA-mRNA Pairs in Embryonic Stem (ES) Cells
Peili Gu5,12#, Jeffrey G. Reid2,6,10#, Xiaolian Gao1,2, Chad A. Shaw7, Chad Creighton9, Peter L. Tran1, Xiaochuan Zhou11, Rafal B. Drabek1,6, David L. Steffen7,8, David M. Hoang1, Michelle K. Weiss1, Arash O. Naghavi1, Jad El-daye1, Mahjabeen F. Khan1, Glen B. Legge1, David A. Wheeler6, Richard A. Gibbs6, Jonathan N. Miller3,6#, Austin J. Cooney5#, Preethi H. Gunaratne1,4,6*
1 Department of Biology & Biochemistry, University of Houston, Houston, Texas, United States of America2 Department of Chemistry, University of Houston, Houston, Texas, United States of America3 Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America4 Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America5 Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America6 Department of Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America7 Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America8 Bioinformatics Research Center, Baylor College of Medicine, Houston, Texas, United States of America9 Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, United States of America10 W. M. Keck Center for Interdisciplinary Bioscience Training, Houston, Texas, United States of America11 LC Sciences, Houston, Texas, United States of America12 Department of Cancer Genetics, M.D. Anderson Cancer Center, University of Texas , Houston, Texas, United States of America
Abstract
Background
MicroRNAs (miRNAs: a class of short non-coding RNAs) are emerging as important agents of post transcriptional gene regulation and integral components of gene networks. MiRNAs have been strongly linked to stem cells, which have a remarkable dual role in development. They can either continuously replenish themselves (self-renewal), or differentiate into cells that execute a limited number of specific actions (pluripotence).
Methodology/Principal Findings
In order to identify novel miRNAs from narrow windows of development we carried out an in silico search for micro-conserved elements (MCE) in adult tissue progenitor transcript sequences. A plethora of previously unknown miRNA candidates were revealed including 545 small RNAs that are enriched in embryonic stem (ES) cells over adult cells. Approximately 20% of these novel candidates are down-regulated in ES (Dicer−/−) ES cells that are impaired in miRNA maturation. The ES-enriched miRNA candidates exhibit distinct and opposite expression trends from mmu-mirs (an abundant class in adult tissues) during retinoic acid (RA)-induced ES cell differentiation. Significant perturbation of trends is found in both miRNAs and novel candidates in ES (GCNF−/−) cells, which display loss of repression of pluripotence genes upon differentiation.
Conclusion/Significance
Combining expression profile information with miRNA target prediction, we identified miRNA-mRNA pairs that correlate with ES cell pluripotence and differentiation. Perturbation of these pairs in the ES (GCNF−/−) mutant suggests a role for miRNAs in the core regulatory networks underlying ES cell self-renewal, pluripotence and differentiation.
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