Suchergebnisse

scRNA-seq data for this project has been deposited in ArrayExpress under the accession numbers E-MTAB-6072 and E-MTAB-7311. Processed data can be found in https://figshare.com/projects/Treg_scRNA-seq/38864, and analysis notebooks can be found in https://github.com/tomasgomes/Treg_analysis. ; Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Subpopulation pseudotime ordering and gene kinetics were consistent in recruitment to skin and colon, yet the initial NLT-priming in LNs and the final stages of NLT functional adaptation reflected tissue-specific differences. Predicted kinetics were recapitulated using an in vivo melanoma-induction model, validating key regulators and receptors. Finally, we profiled human blood and NLT Treg and Tmem cells, and identified cross-mammalian conserved tissue signatures. In summary, we describe the relationship between Treg cell heterogeneity and recruitment to NLTs through the combined use of computational prediction and in vivo validation. ; Wethank V. Proserpio, M. Stubbington, T. Hagai, F.V. Braga, V. Svensson, and J. Henriksson for helpful discussions and advice; T. Hagai, R. Vento-Tormo, K. Meyer, and J. Park for critical reading of the manuscript; and B. Koppelman for editorial support. We thank WSI Single-cell Genomic Core Facility, WSI Sequencing Facility, WSI Flow Cytometry facilities, K. Polanski, and the Kennedy Institute Flow Cytometry Facility for expert technical advice and assistance. R.J.M. was supported by a PhD Fellowship from the Fundação para a Ciência e Tecnologia, Portugal (SFRH/BD/51950/2012) and T.G. by the European Union's H2020 research and innovation program ''ENLIGHT-TEN'' under the Marie Sklodowska-Curie grant ...