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MicroRNAs' Role in Hematopoietic Lineage Differentiation

MicroRNA 在造血谱系分化中的作用

基本信息

批准号：
7651143
负责人：
CHANG-ZHENG CHEN
金额：
$ 37.9万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7651143
关键词：
Address Affect Animals Apoptosis B cell differentiation B-Lymphocytes Base Sequence Biological Assay Biological Process Bone Marrow Breathing Caenorhabditis elegans Candidate Disease Gene Cell Culture Techniques Cell physiology Cells Development Drosophila genus Ectopic Expression Engineering Functional RNA Gene Expression Gene Expression Regulation Gene Targeting Generations Genes Growth Hematological Disease Hematopoiesis Hematopoietic Hematopoietic stem cells Human In Vitro Laboratories Lead Light Link Maintenance Mediating Methods MicroRNAs Molecular Monitor Mus Nematoda Neurons Organ Pattern Plants Play Population Principal Investigator RNA Interference Regulation Regulator Genes Reporter Reporter Genes Research Research Proposals Role Science Signal Pathway Site Small Interfering RNA Stem cells Time Untranslated RNA design expression cloning gene interaction gene repression in vivo insight knock-down leukemia lipid metabolism novel therapeutics plant growth/development prevent research study sensor stem

项目摘要

DESCRIPTION (provided by applicant): The recent discoveries of microRNAs (miRNAs), RNA interference, short interfering RNAs, and small modulatory RNAs have revealed potentially widespread gene regulatory mechanisms that are mediated by short RNAs in animal and plant development. miRNAs are an abundant class of~22 nt endogenous noncoding RNAs. Some have been shown to play an important role in plant and animal development by controlling gene expression at the posttranscriptional level. Recently it was demonstrated that miR-181 could promote B-cell differentiation in vitro and in vivo, providing the first evidence that miRNAs have regulatory roles in vertebrate development (Chen et al., Science, 2004, 303:83). However, examples of miRNAs functioning in vertebrate development are still rare, and the molecular mechanisms through which miRNAs exert their functions are largely unclear. This research proposal addresses these fundamental questions and aims to establish the potential widespread influences of miRNA-mediated posttranscriptional gene regulatory circuitries during hematopoiesis. Through miRNA cloning and expression analyses, we have identified a set of hematopoietic miRNAs that may play important roles in lineage differentiation. We will try to define the functions of these miRNAs in various aspects of hematopoietic lineage differentiation so that we can establish broader roles for miRNAs in hematopoiesis (aim 1). With defined in vitro and in vivo differentiation assays we will be able to dissect the potential signaling pathways that are regulated by miRNAs, determine the structural and functional relationships of miRNA genes, define the progenitor cell population(s) that miRNAs act on, and delineate the cellular processes controlled by miRNAs (aim 2). Finally, we will combine computational and experimental approaches to identify the functionally relevant target genes of hematopoietic miRNAs (aim 3). Understanding the biological functions of miRNAs in hematopoiesis will shed light on the roles of miRNAs in hematological disorders and could lead to novel therapeutic strategies to correct many hematological disorders, including leukemias. The proposed research will also provide methods, insights, and inspiration to those seeking to place miRNAs into other biological processes.

描述（由申请人提供）：最近发现的微小RNA（miRNA）、RNA干扰、短干扰RNA和小调节RNA揭示了在动物和植物发育中由短RNA介导的潜在广泛的基因调控机制。miRNAs是一类丰富的约22 nt的内源性非编码RNA。有些已被证明在植物和动物的发展中发挥重要作用，通过控制基因的表达在转录后水平。最近证明miR-181可以在体外和体内促进B细胞分化，提供了miRNA在脊椎动物发育中具有调节作用的第一个证据（Chen等人，Science，2004，303：83）。然而，miRNA在脊椎动物发育中发挥作用的例子仍然很少，并且miRNA发挥其功能的分子机制在很大程度上尚不清楚。这项研究计划解决了这些基本问题，旨在建立造血过程中miRNA介导的转录后基因调控回路的潜在广泛影响。通过miRNA克隆和表达分析，我们已经确定了一组造血miRNAs，可能在谱系分化中发挥重要作用。我们将尝试定义这些miRNAs在造血谱系分化的各个方面的功能，以便我们可以建立miRNAs在造血中更广泛的作用（目的1）。通过定义的体外和体内分化测定，我们将能够剖析由miRNA调控的潜在信号传导途径，确定miRNA基因的结构和功能关系，定义miRNA作用于的祖细胞群体，并描绘由miRNA控制的细胞过程（目的2）。最后，我们将结合联合收割机的计算和实验方法，以确定造血miRNAs的功能相关的靶基因（目的3）。了解miRNAs在造血中的生物学功能将揭示miRNAs在血液系统疾病中的作用，并可能导致新的治疗策略来纠正许多血液系统疾病，包括白血病。拟议的研究还将为那些寻求将miRNAs置于其他生物过程中的人提供方法，见解和灵感。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identification of the human mature B cell miRNome.

DOI：
10.1016/j.immuni.2009.03.017
发表时间：
2009-05
期刊：
IMMUNITY
影响因子：
32.4
作者：
Basso, Katia;Sumazin, Pavel;Morozov, Pavel;Schneider, Christof;Maute, Roy L.;Kitagawa, Yukiko;Mandelbaum, Jonathan;Haddad, Joseph, Jr.;Chen, Chang-Zheng;Califano, Andrea;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo

Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1/b-1.

DOI：
10.1371/journal.pgen.1002855
发表时间：
2012
期刊：
PLoS genetics
影响因子：
4.5
作者：
Fragoso R;Mao T;Wang S;Schaffert S;Gong X;Yue S;Luong R;Min H;Yashiro-Ohtani Y;Davis M;Pear W;Chen CZ
通讯作者：
Chen CZ

Methods for analyzing microRNA expression and function during hematopoietic lineage differentiation.

分析造血谱系分化过程中 microRNA 表达和功能的方法。