Genomic Profiling of the Inflamed Colon at Single-Cell Resolution

Primary Researchers:

Alex Shalek
Aviv Regev

The objective of this project is to leverage recent advances in single cell and low-input molecular profiling to realize approaches for deeply and thoroughly profiling human gut biopsies and to deploy them to define the normal composition of cell types and states in the gut, as well as the specific changes induced by inflammatory disease, especially inflammatory bowel diseases (IBD).To realize this goal, the Shalek and Regev labs will adapt and couple ultra-low-input RNA-Seq, epigenomic (ATAC-Seq), and proteomic (Immuno-PCR and Proximity Extension Assays) profiling strategies, and apply them to examine normal and inflamed human intestinal gut biopsies, along with matched immune subsets (including intestinal epithelial cells, macrophages, dendritic cells, eosinophils, and T helper cells). In parallel, we will examine histopathology, bacterial burden and derived matched organoids.

For this work, we will obtain consented, de-identified, IRB approved human gut biopsies from the Xavier lab at MGH and then perform cellularization, sorting, single-cell & population RNA-Seq, ATAC-Seq, organoid generation and downstream analyses at MIT and the Broad.