Journal Article

A single-cell survey of the small intestinal epithelium

Herbst, Rebecca H., Biton, Moshe, Smillie, Christopher, Howitt, Michael R., Garrett, Wendy S., Haber, Adam L., Beyaz, Semir, Shi, Hai Ning, Regev, Aviv, Delorey, Toni M., Zhang, Mei, Burgin, Grace, Katz, Yarden, Dionne, Danielle, Rozenblatt-Rosen, Orit, Xavier, Ramnik J., Rogel, Noga, Raychowdhury, Raktima, Shekhar, Karthik, Tirosh, Itay, Yilmaz, Omer

2017

Overview

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. Profiling of 53,193 individual epithelial cells from the mouse small intestine identifies previously unknown cell subtypes and corresponding gene markers, providing insight into gut homeostasis and response to pathogens. Surveying the stomach wall Intestinal epithelial cells can sense and respond to microbial stimuli to support their barrier function and coordinate appropriate immune responses, which range from tolerance to active immunity in cases of pathogen infection. In this study, Aviv Regev, Ramnik Xavier and colleagues used single-cell expression profiling to provide a comprehensive analysis of the epithelial cell composition of mouse small intestines when healthy and after infection, providing new markers, transcriptional programs and organizational principles of gut homeostasis and physiology.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/31 / 13/51 / 38/32 / 45/90 / 45/91 / 631/114/1386 / 631/337/2019 / 631/553/2694 / Abundance / Animals / Bacteria / CD45 antigen / Cell Differentiation / Cytokines - metabolism / Enterocytes / Enterocytes - metabolism / Epithelial cells / Epithelial Cells - cytology / Epithelial Cells - metabolism / Epithelium / Epithelium - metabolism / Female / Gene Expression Profiling / Genes / Genomes / Homeostasis / Humanities and Social Sciences / Immune response / Infections / Intestine, Small - cytology / Leukocyte Common Antigens - metabolism / Male / Mice / multidisciplinary / Nutrients / Organoids / Organoids - cytology / Organoids - metabolism / Paneth cells / Paneth Cells - metabolism / Pathogens / Physiological aspects / Rodents / Salmonella / Science / Single-Cell Analysis / Small intestine / Taxonomy / Thymic stromal lymphopoietin / Transcription factors / Transcription, Genetic