A single-cell survey of the small intestinal epithelium

Adam L. Haber, Moshe Biton (), Noga Rogel, Rebecca H. Herbst, Karthik Shekhar, Christopher Smillie, Grace Burgin, Toni M. Delorey, Michael R. Howitt, Yarden Katz, Itay Tirosh, Semir Beyaz, Danielle Dionne, Mei Zhang, Raktima Raychowdhury, Wendy S. Garrett, Orit Rozenblatt-Rosen, Hai Ning Shi, Omer Yilmaz, Ramnik J. Xavier () and Aviv Regev ()
Additional contact information
Adam L. Haber: Broad Institute of Harvard and Massachusetts Institute of Technology
Moshe Biton: Broad Institute of Harvard and Massachusetts Institute of Technology
Noga Rogel: Broad Institute of Harvard and Massachusetts Institute of Technology
Rebecca H. Herbst: Broad Institute of Harvard and Massachusetts Institute of Technology
Karthik Shekhar: Broad Institute of Harvard and Massachusetts Institute of Technology
Christopher Smillie: Broad Institute of Harvard and Massachusetts Institute of Technology
Grace Burgin: Broad Institute of Harvard and Massachusetts Institute of Technology
Toni M. Delorey: Broad Institute of Harvard and Massachusetts Institute of Technology
Michael R. Howitt: Harvard T. H. Chan School of Public Health
Yarden Katz: Harvard Medical School
Itay Tirosh: Broad Institute of Harvard and Massachusetts Institute of Technology
Semir Beyaz: The David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Massachusetts Institute of Technology
Danielle Dionne: Broad Institute of Harvard and Massachusetts Institute of Technology
Mei Zhang: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School
Raktima Raychowdhury: Broad Institute of Harvard and Massachusetts Institute of Technology
Wendy S. Garrett: Broad Institute of Harvard and Massachusetts Institute of Technology
Orit Rozenblatt-Rosen: Broad Institute of Harvard and Massachusetts Institute of Technology
Hai Ning Shi: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School
Omer Yilmaz: Broad Institute of Harvard and Massachusetts Institute of Technology
Ramnik J. Xavier: Broad Institute of Harvard and Massachusetts Institute of Technology
Aviv Regev: Broad Institute of Harvard and Massachusetts Institute of Technology

Nature, 2017, vol. 551, issue 7680, 333-339

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/nature24489

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