Organ Specific Project Beyond nutrient absorption, the gastrointestinal tract has wide-ranging effects on the normal and diseased physiologies of other organ systems, including metabolism, neural function, and the immune system. A high-resolution map of the bowel would be an invaluable resource to understand normal bowel function and the perturbations that lead to disease. We propose to create this map along the length of the small bowel and colon, both of which have nuanced geographic specializations of function. Using single cell RNA-seq and single cell ATAC-seq, we will profile the gene expression and regulatory programs that define the complex cell populations that drive bowel function. We will use CODEX, a highly-multiplexed, antibody-based mapping method, to define the spatial relationships of these cell populations. These investigations will be performed on tissues that are preserved and procured in a manner suitable for human bowel transplantation. Are target milestone is to characterize the small bowel and colon tissues from a total of 22 individuals over the course of this four-year effort. Our protocol to obtain tissues from human organ donors whose families have provided broad, open access consent is in place, and we are actively collecting tissues for other studies.
