Cellular and inter-cellular rewiring of the human colon during ulcerative colitis
By Chris S. Smillie, Moshe Biton, J. Ordovas-Montañes, Keri M Sullivan, Aviv Regev. Cell, 2019
1,138 citations recorded by the source corpus.
SUMMARY Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4+ enterocytes, microfold-like cells, and IL13RA2+IL11+ inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and co-regulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.
Subfields: Epidemiology, Gastroenterology, Genetics
View Paper: https://www.semanticscholar.org/paper/983afc990c3440cd9e7521daff1bfb1e4702b888
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
- D. Fawkner-Corbett
- A. Antanaviciute
- M. Jagielowicz
- K. Parikh
- A. Gerós
- Tarun Gupta
- N. Ashley
- Doran Khamis
Citations in the corpus
- The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution (2020, neutral): “Although single-cell profiling studies might collect fewer tumors than TCGA, the single-cell resolution addresses compositional confounders (Smillie et al., 2019) and thus helps to reveal disease mechanisms.”
- Spatiotemporal analysis of human intestinal development at single-cell resolution (2021, methodology): “, 2018), and immune (DUOS-000110) (Smillie et al., 2019) data.”
- Spatial components of molecular tissue biology (2022, neutral): “Advances in single-cell profiling have highlighted the aberrations in cell states, compositions and interactions that are associated with disease onset, progression or response to therapy 83,84 and have begun to delineate the coordinated changes across them 34,35 .”
- SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues (2020, neutral): “Massively parallel single-cell RNA-sequencing (scRNA-seq) is transforming our ability to comprehensively map the cell types, subsets, and states present during health and disease in barrier tissues (Ordovas-Montanes et al., 2020; Ordovas-Montanes et al., 2018; Smillie et al., 2019).”