A single-cell survey of the small intestinal epithelium
By Adam L. Haber, Moshe Biton, Noga Rogel, Rebecca H. Herbst, Karthik Shekhar, Chris S. Smillie, Grace Burgin, T. Delorey, Michael R. Howitt, Y. Katz and 11 more. Nature, 2017
1,529 citations recorded by the source corpus.
Intestinal epithelial cells absorb nutrients, respond to microbes, function as a barrier and help to coordinate immune responses. Here we report profiling of 53,193 individual epithelial cells from the small intestine and organoids of mice, which enabled the identification and characterization of previously unknown subtypes of intestinal epithelial cell and their gene signatures. We found unexpected diversity in hormone-secreting enteroendocrine cells and constructed the taxonomy of newly identified subtypes, and distinguished between two subtypes of tuft cell, one of which expresses the epithelial cytokine Tslp and the pan-immune marker CD45, which was not previously associated with non-haematopoietic cells. We also characterized the ways in which cell-intrinsic states and the proportions of different cell types respond to bacterial and helminth infections: Salmonella infection caused an increase in the abundance of Paneth cells and enterocytes, and broad activation of an antimicrobial program; Heligmosomoides polygyrus caused an increase in the abundance of goblet and tuft cells. Our survey highlights previously unidentified markers and programs, associates sensory molecules with cell types, and uncovers principles of gut homeostasis and response to pathogens.
Subfields: Immunology, Nutrition and Dietetics, Surgery
View Paper: https://www.semanticscholar.org/paper/d191eaba338aaf530e41a35266da4c20c5496418
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In Immunology
Citations in the corpus
- Cellular and inter-cellular rewiring of the human colon during ulcerative colitis (2019, methodology): “Cell clustering overview—To cluster single cells into distinct cell subsets, we followed the general procedure outlined in (Haber et al., 2017) with additional modifications.”
- SingleCellNet: a computational tool to classify single cell RNA-Seq data across platforms and across species (2018, background): “, 2017), and to determine how perturbations such as age, pathology, or genetic variation impact cell composition and state (Haber et al., 2017; Kowalczyk et al., 2015; Park et al., 2018; Patel et al., 2014).”
- Feature selection and dimension reduction for single-cell RNA-Seq based on a multinomial model (2019, methodology): “The 10 × Haber dataset [33] was annotated with 12 types of enteroendocrine cells from the intestine.”
- Spatiotemporal analysis of human intestinal development at single-cell resolution (2021, positive): “The final cluster was small intestinal specific and expressed defensins (DEFA5, DEFA6) in keeping with Paneth cells (Haber et al., 2017).”
- Characterization of cell fate probabilities in single-cell data with Palantir (2019, positive): “Diffusion maps have been previously used to study single-cell data 2, 3 and are particularly adept at capturing differentiation trajectories 3, 15 .”
- A gut-brain neural circuit for nutrient sensory transduction (2018, background): “Using mass spectroscopy (seemethods and table S1), we confirmed that enteroendocrine cells express multiple neuropeptides (12, 13), including both cholecystokinin (CCK) and peptide YY (PYY).”