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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 tuftcell, 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 tuftcells. Our survey highlights previously unidentified markers and programs, associates sensory molecules with cell types, and uncovers principles of gut homeostasis and response to pathogens.
The intestinal mucous membrane interacts dynamically with the external environment. Intestinal epithelial cells sense the contents of and pathogens in the gastrointestinal tract and secrete regulatory products that orchestrate appropriate responses. However, we do not yet know all of the discrete types and subtypes of epithelial cell in the gut, their molecular characteristics, how they change during differentiation or how they respond to pathogenic insults.
A survey of RNA profiles of individual intestinal epithelial cells can help to address these questions. Previous surveys that relied on known markers to purify cell populations1,2 cannot always fully distinguish between cell types, might identify only subsets of types in mixed populations or might fail to detect rare cellular populations or intermediate states. Recent studies3-7 attempted to overcome these limitations by using single-cell RNA sequencing (scRNA-seq), but an extensive characterization of intestinal epithelial cellular diversity has yet to be achieved.
Here we perform a scRNA-seq survey of 53,193 epithelial cells of the mouse small intestine in homeostasis and during infection. We identify gene signatures, key transcription factors and specific G-proteincoupled receptors (GPCRs) for each main type of small intestinal differentiated cell. We distinguish proximal and distal enterocytes and their stem cells, establish a...