来自美国休斯顿大学(University of Houston)，贝勒医学院(Baylor College of Medicine)，W. M. Keck Center for Interdisciplinary Bioscience Training(W. M. Keck交叉学科生物科学培训中心)，德克萨斯大学(University of Texas)，以及美国LC Sciences公司的研究人员共同发表了题为"Novel MicroRNA Candidates and miRNA-mRNA Pairs in Embryonic Stem (ES) Cells"的论文。
研究人员通过微阵列芯片筛选出545条新的小RNAs，它们在胚胎干细胞中的含量显著高于成年细胞。结合表达谱信息和对miRNA靶标的预测，研究人员发现了一系列miRNA-mRNA pairs与ES细胞的多功能化(pluripotence)和分化(differentiation)密切相关，进一步研究揭示出miRNA在调控ES细胞的自我更新(self-renewal)、多功能化和分化的核心网络中起着重要的作用。（生物谷Bioon.com）
生物谷推荐原始出处：
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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