GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO

海胆胚胎特定细胞类型的全球基因调控网络

• 批准号: 8288724
• 负责人: ERIC H DAVIDSON
• 金额: $ 58.13万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8288724
• 关键词: Adult; Animals; Bioinformatics; Biological Models; Biological Process; Cell Lineage; Cell physiology; Cells; Cellular biology; Clinical; Code; Complementary DNA; Complex; Conserved Sequence; Development; Developmental Gene; Disease; Effector Cell; Embryo; Endoderm; Endoderm Cell; Excision; Fluorochrome; Gene Expression; Gene Expression Profile; Genes; Genomics; Immune; Instruction; Intergenic Sequence; Knock-in Mouse; Knowledge; Learning; Life; Link; Measurement; Mediating; Mesoderm; Methods; Morphogenesis; Natural Immunity; Oral; Pattern Formation; Physiological; Population; Primitive foregut structure; Problem Solving; Procedures; Process; Proteins; Proxen; Recovery; Regulator Genes; Research; Sea Urchins; Sequence Analysis; Signaling Molecule; Site; Solid; Solutions; Staging; Structure; System; Technology; Time; To specify; Validation; Work; abstracting; blastomere structure; cell type; egg; embryo cell; gastrulation; genome sequencing; interest; network models; research study; success; transcription factor

GLOBAL GENE REGULATORY NETWORKS FOR SPECIFIC CELL TYPES OF THE SEA URCHIN EMBRYO ABSTRACT All developmental, morphogenetic, and differentiation functions of animal cells are executed by large, specifically deployed batteries and cassettes of downstream protein coding genes. A major success of bioscience in recent years has been system level elucidation of the upstream gene regulatory networks (GRNs) that control pattern formation and determine development of the body plan. GRNs consist of genes encoding transcription factors and signaling molecules, plus the transcriptional linkages among these genes, and they determine the regulatory state of every cell at every point in developmental time. Therefore they include the control inputs into all the downstream genes that do the work of the cell. But an enormously important gap in understanding now separates the upstream GRNs that we are beginning to learn about from the downstream effectors of cell function: What is the actual control circuitry that determines the deployment of these downstream genes? How, exactly, are GRNs causally connected to cellular functions of differentiation and morphogenesis? In principle, given knowledge of the upstream GRN and various newly available technology, this gap can be closed, and the problem solved at a system level, and this is the particular object of the present proposal. We will choose three cell types of the developing sea urchin embryo, each of general interest. Knowledge of the upstream GRNs of this embryo is more advanced than for any other system. The target cell types are the immune cells of the embryo, where the downstream effector genes encode a great variety of innate immunity proteins; gastrulating endoderm cells, where the downstream genes mediate gastrular invagination; and the totipotent set-aside cells of the embryonic coelomic pouches that in larval stage produce the adult body plan, where the downstream effector cells include those that maintain totipotency. Innate immunity, gastrular invagination, and totipotent cell lineages are all pan-bilaterian features. The approach, briefly, will be isolation of each cell type using specific regulatory gene expression and FACS; deep transcriptome sequencing; bioinformatic prediction; and validation of causal regulatory connections to specifically expressed genes by high throughput cis- regulatory analysis. This project will provide the first global upstream-downstream GRN for any developing system. It will inform as to basic principles by which downstream gene cassettes are organized. It will also serve as a technological demonstration project for similar approaches to mammalian systems.

海洋特定细胞类型的全球基因调控网络 海胆胚胎 抽象的 动物细胞的所有发育、形态发生和分化功能都是由大的、 专门部署了下游蛋白质编码基因的电池和盒。的重大成功 近年来生物科学一直在系统水平阐明上游基因调控网络 （GRN）控制模式形成并确定身体计划的发展。 GRN 由基因组成 编码转录因子和信号分子，以及这些分子之间的转录联系 基因，它们决定每个细胞在发育时间每个点的调节状态。所以 它们包括对所有执行细胞工作的下游基因的控制输入。但一个巨大的 现在，我们开始了解的上游 GRN 之间存在着巨大的理解差距 来自细胞功能的下游效应器：决定细胞功能的实际控制电路是什么？ 这些下游基因的部署？ GRN 与细胞功能究竟有何因果关系 分化和形态发生？原则上，考虑到上游 GRN 和各种 新的可用技术，可以弥补这一差距，并在系统级别解决问题，这就是 本提案的具体目标。我们将选择发育中的海胆的三种细胞类型 胚胎，每个人都普遍感兴趣。关于该胚胎上游 GRN 的知识比 对于任何其他系统。靶细胞类型是胚胎的免疫细胞，其中下游 效应基因编码多种先天免疫蛋白；原肠胚内胚层细胞，其中 下游基因介导原胃内陷；以及胚胎的全能预留细胞 体腔袋在幼虫阶段产生成虫身体计划，其中下游效应细胞 包括那些保持全能性的。先天免疫、胃内陷和全能细胞谱系 都是泛双边特征。简而言之，该方法将使用特定的方法分离每种细胞类型 调控基因表达和 FACS；深度转录组测序；生物信息预测；和 通过高通量顺式验证与特定表达基因的因果调控关系 监管分析。该项目将为任何发展中国家提供第一个全球上下游GRN 系统。它将告知下游基因盒组织的基本原理。它还将 作为哺乳动物系统类似方法的技术示范项目。