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Nature. 2017 Nov 16;551(7680):333-339. doi: 10.1038/nature24489. Epub 2017 Nov 8.

A single-cell survey of the small intestinal epithelium.

Author information

1
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
2
Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
3
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02114, USA.
4
Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, Massachusetts 01609, USA.
5
Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
6
The David H. Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
7
Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
8
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
9
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
10
Departments of Pathology, Gastroenterology, and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
11
Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
12
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02140, USA.

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.

PMID:
29144463
PMCID:
PMC6022292
DOI:
10.1038/nature24489
[Indexed for MEDLINE]
Free PMC Article

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