Comprehensive gene and microRNA expression profiling reveals a role for microRNAs in human liver development.
Comprehensive gene and microRNA expression profiling reveals a role for microRNAs in human liver development.
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DOI：
10.1371/journal.pone.0007511
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发表时间：
2009-10-20
期刊：
影响因子：
3.7
通讯作者：
Galun E
中科院分区：
文献类型：
--
作者：
Tzur G;Israel A;Levy A;Benjamin H;Meiri E;Shufaro Y;Meir K;Khvalevsky E;Spector Y;Rojansky N;Bentwich Z;Reubinoff BE;Galun E
MicroRNAs(MiRNAs)是一种小的非编码RNAs，在转录后调节同源mRNAs。MiRNAs参与调节胚胎发育过程中的基因表达，包括增殖和分化。肝脏是一个多功能器官，在发育过程中经历快速变化，依赖于严格调控的基因表达。关于人类肝脏发育早期mRNAs和miRNAs的复杂表达模式，人们知之甚少，也没有研究miRNAs在这一过程中的调节作用。这项工作的目的是研究miRNAs对人类肝脏早期发育过程中基因表达的影响。利用高密度微阵列和定量RT-PCR技术，对成体和9-12周人胚胎肝脏的基因和miRNA的表达进行了研究。胚胎肝脏样本表现出随着发育过程的进展而分化的基因表达谱，并揭示了多个调节基因。MiRNA表达谱揭示了与受调控的miRNAs的已知功能相关的四种主要表达模式。使用一种新的算法将受调控最多的miRNAs的表达与其假定的靶标进行比较，发现几个miRNAs的表达存在显著的反相关性，并确定了在胚胎和成年肝脏中最活跃的miRNAs。此外，我们的算法还有助于将转化生长因子β-R1作为LET-7的一个新的靶基因。我们的结果揭示了人类肝脏发育过程中的多个受调控的miRNAs和基因，我们的算法有助于识别在肝脏发育中具有潜在作用的新的miRNA靶标。
microRNAs (miRNAs) are small noncoding RNAs that regulate cognate mRNAs post-transcriptionally. miRNAs have been implicated in regulating gene expression in embryonic developmental processes, including proliferation and differentiation. The liver is a multifunctional organ, which undergoes rapid changes during the developmental period and relies on tightly-regulated gene expression. Little is known regarding the complex expression patterns of both mRNAs and miRNAs during the early stages of human liver development, and the role of miRNAs in the regulation of this process has not been studied. The aim of this work was to study the impact of miRNAs on gene expression during early human liver development. Global gene and miRNA expression were profiled in adult and in 9–12w human embryonic livers, using high-density microarrays and quantitative RT-PCR. Embryonic liver samples exhibited a gene expression profile that differentiated upon progression in the developmental process, and revealed multiple regulated genes. miRNA expression profiling revealed four major expression patterns that correlated with the known function of regulated miRNAs. Comparison of the expression of the most regulated miRNAs to that of their putative targets using a novel algorithm revealed a significant anti-correlation for several miRNAs, and identified the most active miRNAs in embryonic and in adult liver. Furthermore, our algorithm facilitated the identification of TGFβ-R1 as a novel target gene of let-7. Our results uncover multiple regulated miRNAs and genes throughout human liver development, and our algorithm assists in identification of novel miRNA targets with potential roles in liver development.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.3
作者：
Einstein, M;Monga, SPS;Deng, CX
通讯作者：
Deng, CX
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP
影响因子：
30.8
作者：
Krek, A;Grun, D;Rajewsky, N
通讯作者：
Rajewsky, N