Cellular Decisions of Differentiation in the GI Tract

计划项目拨款(PPG)，“胃肠道分化的细胞决定”整合了这些努力 密歇根大学三个系的四名研究人员(两名基础科学研究人员和两名临床研究人员) 医学院。PPG中提出的工作的中心目标是：(A)了解上皮细胞如何在 上胃肠道获得了它们的同一性，两者都是关于组织同一性(胃与小 在个体发育过程中(肠细胞)和谱系特征(肠内分泌细胞与肠细胞或杯状细胞)； 研究胃酸分泌上皮的细胞分化模式是如何正常的 通过特定的细胞内途径控制，以及这些途径是如何被病理侮辱改变的 (这种侮辱可能导致胃上皮细胞特性的改变，以至于它获得了一个小肠 表现力)。子项目#1研究了控制肠道上皮细胞特性的顺式和反式因子， 从特定组织的观点(胃与肠)、区域观点(十二指肠与远端肠道)和 区分的观点(隐窝与尖端)。此外，结合次级项目#2和#4，问题 当胃细胞获得肠道特性(肠化生)后，基因调控如何变化 病理性侮辱将被检查。子项目#2将跟踪肠内分泌细胞的发育 肠内血统，使用CCK作为该细胞室的早期标记。这部作品 将利用在子项目1中产生的受监管的转基因。子项目3将侧重于如何内源性 胃中存在的生长因子控制着壁细胞的分化模式。子项目#4 检查胃上皮对炎症和/或细菌作出反应的途径 通过肠化生在胃中过度生长，这是一种胃细胞特性的改变； 将审查在分项目#3中确定的路径的作用。两个核心将协助PPG调查人员 在细胞生物学技术的表现(核心A)和与计划的管理(核心B)。两者都有 核心将加强这四名调查员在各部门之间已经很强的互动。 总体而言，这个PPG应用程序将进一步加深我们对细胞如何做出身份和 在胃和肠道的分化，并将提供线索，这一身份可能是如何 在病理状态下改变的。

The Program Project Grant (PPG)," Cellular Decisions of Differentiation in the GI Tract" integrates the efforts of four investigators (two basic science and two clinical) from three Departments of the University of Michigan Medical School. The central goals of the work proposed in the PPG are: (a) To understand how epithelial cells in the upper gastrointestinal tract acquire their identity, both both with respect to tissue identity (gastric vs. small intestine) and lineage identity (enteroendocrine cell vs. enterocyte or goblet cell) during ontogeny; (b) To investigate how the patterns of cellular differentiation in the acid-secreting epithelium of the stomach are normally controlled through specific intracellularpathways and how these pathways are altered by pathological insults (such insults can cause an alteration in identity of the gastric epithelium, such that it acquires a small intestinal phenoytpe). Subproject #1 examines the cis and trans factors that control identity in the intestinal epithelial cell, from a tissue-specific standpoint (stomach vs intestine), a regional standpoint (duodenum vs. distal intestine)and a differentiation standpoint (crypt vs.tip). In addition, in conjunction with Subprojects #2 and #4, the question of how gene regulation changes when stomach cells acquire intestinal identity (intestinal metaplasia) after pathological insultwill be examined. Subproject #2 will trace the development of the enteroendocrine cell lineage within the intestine using cholecystokinin (CCK) as an early marker for this cell compartment. This work will utilize regulatory transgenes generated in Subproject #1. Subproject #3 will focus on how endogenous growth factors present in the stomach control the pattern of differentiation of the parietal cell. Subproject #4 examines the pathways through which the gastric epithelium responds to inflammation and/or bacterial overgrowth in the stomach throughthe generation of intestinal metaplasia, an alteration in gastric cell identity; the role of the pathways identified in Subproject #3 will be examined. Two Cores will assist the PPG investigators in the performance of Cell Biology techniques (Core A) and with Administration of the program (Core B). Both Cores will enhance the already strong interaction between these four investigators across Departmental lines. Overall, this PPG application will further our understanding of how cells make decisions of identity and differentiation in the stomach and intestine of the GI tract and will provide clues as to how this identity may be altered in pathological states.