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

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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.