生物
染色质
关贸总协定3
转录组
转录因子
Cd4 t细胞
细胞生物学
T细胞受体
CD8型
表型
免疫系统
细胞毒性T细胞
遗传学
作者
Evgeny Kiner,Elijah Willie,Brinda Vijaykumar,Kaitavjeet Chowdhary,Hugo Schmutz,Jodie Chandler,Alexandra Schnell,Pratiksha I. Thakore,Graham LeGros,Sara Mostafavi,Diane Mathis,Christophe Benoist
标识
DOI:10.1038/s41590-020-00836-7
摘要
CD4+ effector lymphocytes (Teff) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (TH) subsets. At baseline or at different times of infection, transcripts encoding cytokines or proteins commonly used as TH markers were distributed in a polarized continuum, which was functionally validated. Clones derived from single progenitors gave rise to both IFN-γ- and interleukin (IL)-17-producing cells. Most of the transcriptional variance was tied to the infecting agent, independent of the cytokines produced, and chromatin variance primarily reflected activities of activator protein (AP)-1 and IFN-regulatory factor (IRF) transcription factor (TF) families, not the canonical subset master regulators T-bet, GATA3 or RORγ.
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