Klein, L., Kyewski, B., Allen, P. M. & Hogquist, K. A. Positive and negative selection of the T cell repertoire: what thymocytes see (and don’t see). Nat. Rev. Immunol. 14, 377–391 (2014).
Bornstein, C. et al. Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells. Nature 559, 622–626 (2018).
Baran-Gale, J. et al. Ageing compromises mouse thymus function and remodels epithelial cell differentiation. eLife 9, e56221 (2020).
Bautista, J. L. et al. Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla. Nat. Commun. 12, 1096 (2021).
Dhalla, F. et al. Biologically indeterminate yet ordered promiscuous gene expression in single medullary thymic epithelial cells. EMBO J. 39, e101828 (2020).
Park, J. E. et al. A cell atlas of human thymic development defines T cell repertoire formation. Science 367, eaay3224 (2020).
Michelson, D. A., Hase, K., Kaisho, T., Benoist, C. & Mathis, D. Thymic epithelial cells co-opt lineage-defining transcription factors to eliminate autoreactive T cells. Cell 185, 2542–2558 (2022).
Abramson, J. & Anderson, G. Thymic epithelial cells. Annu. Rev. Immunol. 35, 85–118 (2017).
Sansom, S. N. et al. Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia. Genome Res. 24, 1918–1931 (2014).
Anderson, M. S. et al. Projection of an immunological self shadow within the thymus by the Aire protein. Science 298, 1395–1401 (2002).
Metzger, T. C. et al. Lineage tracing and cell ablation identifiy a post-Aire expressing thymic epithelial cell population. Cell Rep. 5, 166–179 (2013).
Miller, C. N. et al. Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development. Nature 559, 627–631 (2018).
Miragaia, R. J. et al. Single-cell RNA-sequencing resolves self-antigen expression during mTEC development. Sci. Rep. 8, 685 (2018).
Miyao, T. et al. Integrative analysis of scRNA-seq and scATAC-seq revealed transit-amplifying thymic epithelial cells expressing autoimmune regulator. eLife 11, e73998 (2022).
Wang, X. et al. Post-Aire maturation of thymic medullary epithelial cells involves selective expression of keratinocyte-specific autoantigens. Front. Immunol. 3, 19 (2012).
Goldstein, J. D. et al. IL-36 signaling in keratinocytes controls early IL-23 production in psoriasis-like dermatitis. Life Sci. Alliance 3, e202000688 (2020).
Wang, W., Yu, X., Wu, C. & Jin, H. IL-36γ inhibits differentiation and induces inflammation of keratinocyte via Wnt signaling pathway in psoriasis. Int. J. Med. Sci. 14, 1002–1007 (2017).
Mabbott, N. A., Donaldson, D. S., Ohno, H., Williams, I. R. & Mahajan, A. Microfold (M) cells: important immunosurveillance posts in the intestinal epithelium. Mucosal Immunol. 6, 666–677 (2013).
Onder, L. et al. Alternative NF-κB signaling regulates mTEC differentiation from podoplanin-expressing precursors in the cortico-medullary junction. Eur. J. Immunol. 45, 2218–2231 (2015).
Wells, K. L. et al. Combined transient ablation and single-cell RNA sequencing reveals the development of medullary thymic epithelial cells. eLife 9, e60188 (2020).
Goldfarb, Y. et al. Mechanistic dissection of dominant AIRE mutations in mouse models reveals AIRE autoregulation. J. Exp. Med. 218, e20201076 (2021).
Borromeo, M. D. et al. ASCL1 and NEUROD1 reveal heterogeneity in pulmonary neuroendocrine tumors and regulate distinct genetic programs. Cell Rep. 16, 1259–1272 (2016).
Osipovich, A. B. et al. Insm1 promotes endocrine cell differentiation by modulating the expression of a network of genes that includes Neurog3 and Ripply3. Development 141, 2939–2949 (2014).
Jia, S. et al. Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function. EMBO J. 34, 1417–1433 (2015).
Henry, C., Close, A.-F. & Buteau, J. A critical role for the neural zinc factor ST18 in pancreatic β-cell apoptosis. J. Biol. Chem. 289, 8413–8419 (2014).
Guo, T. et al. ISL1 promotes pancreatic islet cell proliferation. PLoS One 6, e22387 (2011).
Gehart, H. et al. Identification of enteroendocrine regulators by real-time single-cell differentiation mapping. Cell 176, 1158–1173 (2019).
Fothergill, L. J. et al. Distribution and co-expression patterns of specific cell markers of enteroendocrine cells in pig gastric epithelium. Cell Tissue Res. 378, 457–469 (2019).
Jiang, W., Anderson, M. S., Bronson, R., Mathis, D. & Benoist, C. Modifier loci condition autoimmunity provoked by Aire deficiency. J. Exp. Med. 202, 805–815 (2005).
Tuncel, J., Benoist, C. & Mathis, D. T cell anergy in perinatal mice is promoted by T reg cells and prevented by IL-33. J. Exp. Med. 216, 1328–1344 (2019).
Dixit, V. D. et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J. Clin. Invest. 114, 57–66 (2004).
Dixit, V. D. et al. Ghrelin promotes thymopoiesis during aging. J. Clin. Invest. 117, 2778–2790 (2007).
Kobayashi, N., Takahashi, D., Takano, S., Kimura, S. & Hase, K. The roles of Peyer’s patches and microfold cells in the gut immune system: relevance to autoimmune diseases. Front. Immunol. 10, 2345 (2019).
Kanaya, T. et al. The Ets transcription factor Spi-B is essential for the differentiation of intestinal microfold cells. Nat. Immunol. 13, 729–736 (2012).
Akiyama, N. et al. Limitation of immune tolerance-inducing thymic epithelial cell development by Spi-B-mediated negative feedback regulation. J. Exp. Med. 211, 2425 (2014).
Kimura, S. et al. Osteoprotegerin-dependent M cell self-regulation balances gut infection and immunity. Nat. Commun. 11, 234 (2020).
McCarthy, N. I. et al. Osteoprotegerin-mediated homeostasis of Rank+ thymic epithelial cells does not limit Foxp3+ regulatory t cell development. J. Immunol. 195, 2675–2682 (2015).
Dillon, A. & Lo, D. D. M cells: intelligent engineering of mucosal immune surveillance. Front. Immunol. 10, 1499 (2019).
Wang, J., Gusti, V., Saraswati, A. & Lo, D. D. Convergent and divergent development among M cell lineages in mouse mucosal epithelium. J. Immunol. 187, 5277–5285 (2011).
Komban, R. J. et al. Activated Peyer’s patch B cells sample antigen directly from M cells in the subepithelial dome. Nat. Commun. 10, 2423 (2019).
Sakhon, O. S. et al. M cell-derived vesicles suggest a unique pathway for trans-epithelial antigen delivery. Tissue Barriers 3, e1004975 (2015).
Cerutti, A. The regulation of IgA class switching. Nat. Rev. Immunol. 8, 421–434 (2008).
López-Fraga, M., Fernández, R., Albar, J. P. & Hahne, M. Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase. EMBO Rep. 2, 945–951 (2001).
de Lau, W. et al. Peyer’s patch M cells derived from Lgr5+ stem cells require SpiB and are induced by RankL in cultured ‘miniguts’. Mol. Cell. Biol. 32, 3639–3647 (2012).
Meredith, M., Zemmour, D., Mathis, D. & Benoist, C. Aire controls gene expression in the thymic epithelium with ordered stochasticity. Nat. Immunol. 16, 942–949 (2015).
Lucas, B. et al. Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells. Nat. Commun. 11, 2198 (2020).
Rios, D. et al. Antigen sampling by intestinal M cells is the principal pathway initiating mucosal IgA production to commensal enteric bacteria. Mucosal Immunol. 9, 907–916 (2016).
Kim, Y.-I. et al. CX3CR1+ macrophages and CD8+ T cells control intestinal IgA production. J. Immunol. 201, 1287–1294 (2018).
Reboldi, A. et al. Mucosal immunology: IgA production requires B cell interaction with subepithelial dendritic cells in Peyer’s patches. Science 352, aaf4822 (2016).
Vobořil, M. et al. A model of preferential pairing between epithelial and dendritic cells in thymic antigen transfer. eLife 11, e71578 (2022).
Vollmann, E. H. et al. Specialized transendothelial dendritic cells mediate thymic T-cell selection against blood-borne macromolecules. Nat. Commun. 12, 6230 (2021).
Gardner, J. M. et al. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science 321, 843 (2008).
Su, G. H. et al. Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B. EMBO J. 16, 7118–7129 (1997).
Pacary, E. et al. Proneural transcription factors regulate different steps of cortical neuron migration through rnd-mediated inhibition of RhoA signaling. Neuron 69, 1069–1084 (2011).
Jung, S. et al. Analysis of fractalkine receptor CX3CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol. Cell. Biol. 20, 4106–4114 (2000).
Hsu, P. D. et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat. Biotechnol. 31, 827–832 (2013).
Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34, 184–191 (2016).
Xu, H. et al. Sequence determinants of improved CRISPR sgRNA design. Genome Res 25, 1147–1157 (2015).
Concordet, J. P. & Haeussler, M. CRISPOR: intuitive guide selection for CRISPR/Cas9 genome editing experiments and screens. Nucleic Acids Res. 46, W242–W245 (2018).
Jaitin, D. A. et al. Massively parallel single-cell RNA-seq for marker-free decomposition of tissues into cell types. Science 343, 776–779 (2014).
Kohen, R. et al. UTAP: user-friendly transcriptome analysis pipeline. BMC Bioinformatics 20, 154 (2019).
Stuart, T. et al. Comprehensive integration of Single-cell data. Cell 177, 1888–1902 (2019).
Stuart, T., Srivastava, A., Madad, S., Lareau, C. A. & Satija, R. Single-cell chromatin state analysis with Signac. Nat. Methods 18, 1333–1341 (2021).
Hafemeister, C. & Satija, R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 20, 296 (2019).
Zhang, Y. et al. Model-based Analysis of ChIP–Seq (MACS). Genome Biol. 9, R137 (2008).
Schep, A. N., Wu, B., Buenrostro, J. D. & Greenleaf, W. J. chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data. Nat. Methods 14, 975–978 (2017).
Khan, A. et al. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic Acids Res. 46, D260–D266 (2018).
Boyle, E. I. et al. GO::TermFinder—open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics 20, 3710–3715 (2004).
Kachitvichyanukul, V. & Schmeiser, B. Computer generation of hypergeometric random variates. J. Stat. Comput. Sim. 22, 127–145 (2007).
Benjaminit, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. B 57, 289–300 (1995).
Stoeckius, M. et al. Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics. Genome Biol. 19, 224 (2018).
Jin, S. et al. Inference and analysis of cell–cell communication using CellChat. Nat. Commun. 12, 1088 (2021).
