The roles of regional specialization, mechanical forces and epigenetic memory after perturbation and injury of the intestinal stem cell microenvironment

项目摘要 分析高通量基因组数据，特别是单细胞基因组数据的方法的复杂性增加， 数据集，要求实验和计算科学家之间的紧密互动。分析如何 肠的不同隔室相互作用并对损伤作出反应， 单细胞水平的研究。该项目将加速肠干基因组分析的进展 ISCC成员通过以下两个目标建立细胞生态位，（1）个人项目合作 中心，以及（2）在一个联盟范围内的项目，以确定遗传因素的最小集合的合作 支持人类和小鼠肠道干细胞生态位的比较方法。上一 在这个项目的几年里，我们已经与六个ISCC团队建立了合作关系，以帮助他们的项目;其中一些 这些合作已经完成并出版，其他合作正在进行中，我们将继续 建立新的合作。这个联盟范围的项目的目标是注释一组基因模块 以及人类和小鼠肠道干细胞龛中的通讯模块。我们在分析单个- 细胞基因表达数据集由ISCC实验室生成;小鼠数据由Shivdasani实验室提供， Helmrath实验室的人类数据;我们还将公开可用的数据集整合到我们的分析中。这 该项目将提供一套保守的和衍生的因子，参与维持肠道 干细胞龛和所有间充质、上皮和其它细胞联合体认可命名法 人类和小鼠肠道中的亚型。

Project Summary The increased complexity of methods to analyze high-throughput genomic data, particularly single cell datasets, mandates the tight interaction between experimental and computational scientists. Analysis of how different compartments of the intestine interact with each other and react to insults is greatly advanced by studies at the single cell level. This project will accelerate progress of genomic analysis of the intestinal stem cell niche by ISCC members through the following two aims, (1) collaborations on projects from individual centers, and (2) collaboration on a consortium-wide project to determine the minimum set of genetic factors that support the intestinal stem cell niche in human and mouse using a comparative approach. In the previous years of this project, we have established collaborations with six ISCC teams to help with their project; some of these collaborations have been completed and resulted in publications, others are ongoing, and we continue establishing new collaborations. The consortium-wide project has the goal of annotating a set of gene modules and communication modules in the intestinal stem cell niche in mouse and human. We are analyzing single- cell gene expression datasets generated by ISCC labs; mouse data are provided by the Shivdasani lab, and human data by the Helmrath lab; we are also integrating publicly available datasets into our analysis. This project will deliver a set of conserved and derived factors that participate in the maintenance of the intestinal stem cell niche and a consortium-endorsed nomenclature of all mesenchymal, epithelial, and other cell subtypes in human and mouse intestine.