Comparative genomic and molecular genetics approaches to retinal stem cells

视网膜干细胞的比较基因组和分子遗传学方法

基本信息

  • 批准号:
    7531127
  • 负责人:
  • 金额:
    $ 18.69万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-09-01 至 2010-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): The long term goal of this proposal is to develop therapeutic interventions in the generation of neurons from neural stem cells (NSC) for replacement therapies of disease and injury in the central nervous system (CNS). Neural stem cells give rise to all of the different cell types in the CNS. Understanding of the complex transcriptional networks that control the process of cell fate determination in NSC is crucial in applications for therapeutic purpose. The generation of diversity of neurons and glial cells is achieved through cell proliferation, cell fate determination and differentiation of embryonic NSC populations into progressively more specialized cell types that make up the CNS. The uniqueness of individual neurons and glial cells is determined by combinatorial patterns of gene expression; and gene expression is largely controlled at the level of DNA sequence (cis-regulatory element, genetic), as well as by chromatin structure (epigenetic). One of the key components in transcription regulation is the enhancer, a non-coding DNA sequence that is often evolutionarily conserved. Upon binding of trans-acting factors, enhancers determine tissue or cell type-specific expression of particular genes. We will choose genes that are crucial to NSC cell fate determination from genome wide gene expression studies and analyze the non-coding DNA regions for their regulatory functions (e.g. as an enhancer) in NSC gene expression during cell fate determination. We will predict (in silico) and functionally characterize (in vivo) the predicted putative enhancers in chick retinal stem cells. We refer to this kind of enhancer as NSC enhancers. Our focus will be on NSC enhancers that are important for the development of the retina. The two specific aims are: 1) to predict evolutionarily conserved NSC enhancers; and 2) to verify and characterize putative NSC enhancers. The successful completion of the proposed study will help to identify transcriptional control networks that are crucial for cell fate determination of neural stem cells. In addition, novel retina-specific enhancers identified from this study can be used to identify novel protein factors that are previously unknown for their function in controlling neural cell fate determination. Our findings will ultimately provide an integrated transcription network that controls NSC cell fate determination in the retina (can also be applied to other developmental systems in general). Such an understanding of the transcriptional networks is fundamental to the development of potential treatments or therapeutic transplants for diseases ranging from retinal degeneration to spinal cord injury. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to search for DNA sequence elements that exist in the non-protein coding regions of the genome that regulate the generation of nerve cells from neural stem cells. The successful completion of the proposed studies will help the development of potential treatments or therapeutic transplants for diseases ranging from neural degeneration to spinal cord injury.
描述(由申请人提供):本提案的长期目标是开发从神经干细胞(NSC)生成神经元的治疗干预措施,用于中枢神经系统(CNS)疾病和损伤的替代疗法。神经干细胞在中枢神经系统中产生所有不同的细胞类型。了解复杂的转录网络,控制过程中的细胞命运的决定,在神经干细胞的治疗应用是至关重要的。神经元和神经胶质细胞多样性的产生是通过细胞增殖、细胞命运决定和胚胎NSC群体分化为构成CNS的逐渐更特化的细胞类型来实现的。单个神经元和神经胶质细胞的独特性是由基因表达的组合模式决定的;基因表达在很大程度上控制在DNA序列水平(顺式调控元件,遗传),以及染色质结构(表观遗传)。转录调控的关键成分之一是增强子,一种通常在进化上保守的非编码DNA序列。在结合反式作用因子后,增强子决定特定基因的组织或细胞类型特异性表达。我们将从全基因组基因表达研究中选择对NSC细胞命运决定至关重要的基因,并分析非编码DNA区域在细胞命运决定期间NSC基因表达中的调控功能(例如作为增强子)。我们将预测(在硅片上)和功能特性(在体内)预测推定的增强子在鸡视网膜干细胞。我们将这种增强子称为NSC增强子。我们的重点将放在对视网膜发育重要的NSC增强剂上。两个具体的目的是:1)预测进化保守的NSC增强子;和2)验证和表征推定的NSC增强子。这项研究的成功完成将有助于确定对神经干细胞的细胞命运决定至关重要的转录控制网络。此外,从本研究中鉴定的新型视网膜特异性增强子可用于鉴定以前未知的在控制神经细胞命运决定中的功能的新型蛋白质因子。我们的研究结果最终将提供一个集成的转录网络,控制视网膜中NSC细胞的命运决定(也可以应用于一般的其他发育系统)。对转录网络的这种理解对于开发从视网膜变性到脊髓损伤的疾病的潜在治疗或治疗性移植是基础。 公共卫生相关性:这项计划的目标是寻找存在于基因组非蛋白质编码区的DNA序列元件,这些元件调节神经干细胞产生神经细胞。拟议研究的成功完成将有助于开发从神经变性到脊髓损伤等疾病的潜在治疗或治疗性移植。

项目成果

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Li Cai其他文献

Li Cai的其他文献

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{{ truncateString('Li Cai', 18)}}的其他基金

Measurement of Recovery from Drug Addiction LC
吸毒成瘾恢复的测量 LC
  • 批准号:
    8138410
  • 财政年份:
    2010
  • 资助金额:
    $ 18.69万
  • 项目类别:
Measurement of Recovery from Drug Addiction LC
吸毒成瘾恢复的测量 LC
  • 批准号:
    8307470
  • 财政年份:
    2010
  • 资助金额:
    $ 18.69万
  • 项目类别:
Identification and characterization of genetic regulators in cancer stem cell
癌症干细胞遗传调节因子的鉴定和表征
  • 批准号:
    7672533
  • 财政年份:
    2008
  • 资助金额:
    $ 18.69万
  • 项目类别:
Identification and characterization of genetic regulators in cancer stem cell
癌症干细胞遗传调节因子的鉴定和表征
  • 批准号:
    7532339
  • 财政年份:
    2008
  • 资助金额:
    $ 18.69万
  • 项目类别:
Comparative genomic and molecular genetics approaches to retinal stem cells
视网膜干细胞的比较基因组和分子遗传学方法
  • 批准号:
    7677879
  • 财政年份:
    2008
  • 资助金额:
    $ 18.69万
  • 项目类别:

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