Informatics and Data Management Core

胃肠道(Gl)神经肌肉疾病以运动功能障碍为特征。GL运动主要是 受三种神经效应细胞的调节，即平滑肌细胞(SMCs)，Cajal间质细胞(ICC)， 以及PDGFRA+信元，所有这些信元都电耦合以形成称为SIP的综合网络 合胞体。为了了解Gl运动，应该一起研究SIP细胞，因为这些细胞中的每一个 修改其他单元格的行为。该计划试图发现SIP信元中的各种元素 以有益或病理的方式影响Gl运动：1)起搏器活动的分子机制和 对神经传递反应的调节；2)嘌呤信号和代谢途径；以及3) C-kit表达缺失和恢复后ICC的表型和遗传变化。这些项目中的每个 将与核心提供的信息学和数据管理能力互动。核心员工 下一代测序(mRNA-seq)，提供每种SIP细胞类型在 全基因组范围和非常高的分辨率。全基因组的转录本将提供所有的基因，亚型， 以及在每种细胞类型中表达的剪接变体。此外，他们还将确定以下方面的变化 单个基因、异构体和剪接变异体的表达水平在病理上具有更高的分辨率 更改了SIP信元。这种强大的全基因组研究基因表达的方法将揭示：1) SIP细胞整个转录组的变化；2)确定细胞特异性基因、异构体和剪接变异体； 3)检查单个转录本以进行功能研究；4)将转录信息与潜在的 细胞的生理功能；以及5)确定控制细胞表型变化的基因。 相关性(请参阅说明)： 对sip细胞转录组研究中预期的重要元素的发现将 提供路线图，以详细研究每种细胞类型的功能，并帮助开发 将发展为人体研究的假设，这将刺激临床治疗学的发展 治疗患有运动障碍的人类受试者，这些细胞类型可能与病理有关。

Gastrointestinal (Gl) neuromuscular disorders are characterized by motility dysfunctions. Gl motility is mainly regulated by three types of neuro-effector cells, Smooth muscle cells (SMCs), Interstitial cells of Cajal (ICC), and PDGFRa+ cells, all of which are electrically coupled to form the integrated network referred as SIP syncytium. To understand Gl motility, SIP cells should be studied together because each of these cells modifies the behaviors ofthe other cells. This Program seeks to uncover a variety of elements in SIP cells that affect Gl motility in beneficial or pathological ways: 1) molecular mechanisms of pacemaker activity and regulation of responses to neurotransmission; 2) purine signaling and metabolism pathways; and 3) phenotypic and genetic changes of ICC after loss and restoration of c-KIT expression. Each of these projects will interact with the informatics and data management capabilities provided by the Core. The Core employs next-generation sequencing (mRNA-seq) that provides gene expression profiles of each SIP cell type on a genome-wide scale with very high resolution. The genome-wide transcripts will provide all genes, isoforms, and splice variants that are expressed in each cell type. In addition, they will also identify changes in expression levels for individual genes, isoforms, and splice variants with superior resolution in pathologically changed SIP cells. This powerful genome-wide approach to study gene expression will reveal: 1) patterns of changes in the entire transcriptome of SIP cells; 2) identify cell-specific genes, isoforms, and splice variants; 3) examine individual transcripts for functional studies; 4) link transcriptional information to potential physiologic functions ofthe cells; and 5) identify genes that control phenotypic changes ofthe cells. RELEVANCE (See instructions): The discovery of important elements that are anticipated with the transcriptome study ofthe SIP cells will provide a road map to study in detail the functions of each cell type and aid in the development of hypotheses that will progress to human studies, which will stimulate the development of clinical therapeutics to treat human subjects with motility disorders where these cell types may be pathologically involved.