| Literature DB >> 30392957 |
Moshe Biton1, Adam L Haber2, Noga Rogel2, Grace Burgin2, Semir Beyaz3, Alexandra Schnell4, Orr Ashenberg2, Chien-Wen Su5, Christopher Smillie2, Karthik Shekhar2, Zuojia Chen4, Chuan Wu4, Jose Ordovas-Montanes6, David Alvarez7, Rebecca H Herbst8, Mei Zhang5, Itay Tirosh9, Danielle Dionne2, Lan T Nguyen2, Michael E Xifaras10, Alex K Shalek6, Ulrich H von Andrian7, Daniel B Graham11, Orit Rozenblatt-Rosen2, Hai Ning Shi5, Vijay Kuchroo12, Omer H Yilmaz13, Aviv Regev14, Ramnik J Xavier15.
Abstract
In the small intestine, a niche of accessory cell types supports the generation of mature epithelial cell types from intestinal stem cells (ISCs). It is unclear, however, if and how immune cells in the niche affect ISC fate or the balance between self-renewal and differentiation. Here, we use single-cell RNA sequencing (scRNA-seq) to identify MHC class II (MHCII) machinery enrichment in two subsets of Lgr5+ ISCs. We show that MHCII+ Lgr5+ ISCs are non-conventional antigen-presenting cells in co-cultures with CD4+ T helper (Th) cells. Stimulation of intestinal organoids with key Th cytokines affects Lgr5+ ISC renewal and differentiation in opposing ways: pro-inflammatory signals promote differentiation, while regulatory cells and cytokines reduce it. In vivo genetic perturbation of Th cells or MHCII expression on Lgr5+ ISCs impacts epithelial cell differentiation and IEC fate during infection. These interactions between Th cells and Lgr5+ ISCs, thus, orchestrate tissue-wide responses to external signals.Entities:
Keywords: ISCs; MHC class II; MHCII; T helper; T regulatory; T(reg); Th; epithelial differentiation; gut biology; intestinal stem cells; mucosal immunity; scRNA-seq; single cell RNA-seq; stem cell renewal; tuft cells
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Year: 2018 PMID： 30392957 PMCID： PMC6239889 DOI： 10.1016/j.cell.2018.10.008
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582