Overall The small bowel and colon are organs critical for maintaining homeostasis of the human body by mediating nutritional absorption upon the ingestion of food. Though both organs are extensive in length, there are known differences in function and cellular heterogeneity within different portions of each. Also, a cross section anywhere in the bowel reveals a complex layering of components involved in absorption and secretion, motility of gut contents, circulation, and immunity. In this submission, we propose the establishment of the Stanford Tissue Mapping Center (TMC) to map the complexity of the the small bowel and colon with cell-to-cell resolution in histologic sections, both along their lengths and across multiple individuals. To accomplish this goal, we will collect tissues from brain-dead organ donors with explicit consent for distribution among the HuBMAP consortium and open access genome data sharing (GDS). Two sets of technologies will then be employed. Tissue samples will be subjected to single cell (sc) ATAC-seq and scRNA-seq. These ?omic profiles will then be spatially mapped back to histologic sections using a highly multiplexed system of antibody-tagged target epitopes, which we call CO-Detection by indEXing (CODEX). An integrative analysis will be performed to identify proteins important to establishing the identity of each cell population within the tissue. ?
Overall We propose to establish the Stanford Tissue Mapping Center to map the complexity of cellular architecture and biomolecular profiles of the small bowel and colon, which play wide-ranging roles in maintaining normal physiologies of metabolism, immunity, and even neural function. We will apply the deep expertise of our team to obtain high-quality biospecimens consented for open access genome data sharing, characterize the tissues using cutting-edge omics and multiparametric imaging techniques, and perform integrative analyses to understand the biomolecular profiles in the context of spatial tissue structure. We will build high-resolution, molecular and spatial maps that will give the greater scientific community insights into the molecular underpinnings of normal bowel function.
