Poster #69: Katherine Beigel MS

A single-cell meta-atlas of human intestinal smooth muscle cells (HISMCs) in intestinal diseases

Katherine Beigel (MS)1, Sharon M. Wolfson (MD)2,3, Robert O. Heuckeroth (MD, PhD)2,3 Affiliations: 1The Department of Biomedical and Health Informatics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA 2The Children’s Hospital of Philadelphia Research Institute and the Abramson Research Center, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA 3Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

There are numerous publicly available single-cell RNA sequencing and single-nuclei RNA-sequencing datasets of the human intestines. While the original studies that published these datasets were primarily focused on immune cells, intestinal epithelial cells, or other disease-relevant cell populations, the smooth muscle cells (SMCs) within these datasets have not been analyzed in detail. SMCs are essential for gastrointestinal motility, and SMC function may be altered by inflammation and other pathological processes that occur in intestinal disease states. Intestinal diseases including Hirshsprung’s disease, inflammatory bowel diseases (Chron’s disease, ulcerative colitis), and celiac disease are associated with intestinal dysfunction and altered gastrointestinal motility. This suggests that SMCs may play a role in these disease pathways, but the underlying cellular and molecular mechanisms of SMCs in human intestinal diseases are not completely understood. In this study, we aim to build a meta-atlas of publicly available scRNA-seq and snRNA-seq datasets containing human intestinal SMCs (HISMCs) from intestinal tissue of diseased and control individuals. Our approach combines multiple different datasets and harmonizes the data to reduce batch effects from different sequencing platforms, tissue types, cell isolation methods, and other study-specific variables. By integrating datasets from published studies that contain a variety of intestinal disease states, we aim to characterize conserved and disease-specific gene expression patterns in SMCs. Constructing a meta-altas in this manner will allow us to identify variations and similarities in the transcriptional profiles of SMCs across multiple intestinal diseases. Our goal is to use this information to provide new insights about how SMCs may contribute to or be affected by gastrointestinal dysfunction across intestinal diseases.