Cellular Decisions of Differentiation in the GI Tract

描述(由申请人提供)： 该计划项目拨款(PPG)“胃肠道分化的细胞决定”整合了来自密歇根大学医学院三个系的三名研究人员(一名基础科学和两名临床)的努力。拟议研究的中心目标是：(A)了解胃上皮细胞如何通过表达或响应多肽形态原Sonic Hedgehog(Shh)来发育和维持其特性(B)研究胃分泌酸性上皮中的细胞分化模式如何随着病理损伤(例如炎症)的反应而改变(这种损伤可以改变胃上皮的特性，使其获得小肠表型)。题为“胃祖细胞亚群的生物学”的子项目1将研究胚胎中胃祖细胞(干细胞)发育的时间进程，以及它们对Shh或促炎症细胞因子干扰素-γ的反应。子项目2题为“Hedgehog Signals in Hedgehog Signals in Get Hedgehog Homostance and病理学”，将使用LacZ报告小鼠来识别和表征表达Hedgehog信号并对Hedgehog信号做出反应的胃细胞群。此外，还将分析Hedgehog信号如何介导上皮-间充质串扰。题为《胃部刺猬的作用是正常的和发炎的》的子项目#3将重点放在如何从壁细胞产生生物活性Shh并调节体腔-胃窦的串扰。所有项目都专注于解剖胃内的发育途径，并广泛使用小鼠模型来询问主要与Shh有关的重要信号通路。两个核心将协助PPG调查员--细胞生物学(核心A)和行政(核心B)。细胞生物学核心将促进使用最先进的成像和生物信息学技术分析老鼠模型。行政核心将通过组织每月联席会议和共同赞助特邀演讲者，加强这三名调查员在各部门之间已经很强的互动。这将进一步加深我们对胃细胞如何做出身份和分化决定的理解，并提供与公共健康相关的炎症信号如何改变其表型的线索。

DESCRIPTION (provided by applicant): The Program Project Grant (PPG), "Cellular Decisions of Differentiation in the Gl Tract" integrates the efforts of three investigators (one basic science and two clinical) from three Departments at the University of Michigan Medical School. The central goals of the proposed studies are: (a) To understand how gastric epithelial cells develop and maintain their identity by expressing or responding to the peptide morphogen sonic hedgehog (Shh) (b) To investigate how the patterns of cellular differentiation in the acid-secreting epithelium of the stomach changes in response to pathological insults, e.g., inflammation (such insults can alter the identity of the gastric epithelium, such that it acquires a small intestinal phenotype). Subproject 1 entitled "Biology of a Sub-population of Gastric Progenitor Cells" will examine the time course of gastric progenitor (stem) cell development in the embryo and their response to Shh or the proinflammatory cytokine interferon gamma. Subproject #2 entitled, "Hedgehog signaling in stomach homeostasis and pathology," will use LacZ reporter mice to identify and characterize the gastric cell populations that express and respond to hedgehog signals. In addition, how hedgehog signals mediate the epithelial-mesenchymal crosstalk will be analyzed. Subproject #3 entitled "Role of Parietal Cell Hedgehog is normal and Inflamed Stomach," will focus on how biologically active Shh is generated from the parietal cell and mediates corpus-antral crosstalk. All projects focus on dissecting developmental pathways in the stomach and make extensive use of mouse models to interrogate important signaling pathways primarily related to Shh. Two Cores will assist the PPG investigators-the Cell Biology (Core A) and the Administrative (Core B). The Cell Biology Core will facilitate the analysis of the mouse models using state-of-the-art imaging and bioinformatics techniques. The Administrative Core will enhance the already strong interaction between these three investigators across department lines by organizing monthly joint meetings and co-sponsoring invited speakers. This will further our understanding of how gastric cells make decisions of identity and differentiation and provide clues on how their phenotype is altered by inflammatory signals as relevant to public health.