Chapter title |
Revelations in Thymic Epithelial Cell Biology and Heterogeneity from Single-Cell RNA Sequencing and Lineage Tracing Methodologies.
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Chapter number | 2 |
Book title |
T-Cell Development
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Published in |
Methods in molecular biology, January 2023
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DOI | 10.1007/978-1-0716-2740-2_2 |
Pubmed ID | |
Book ISBNs |
978-1-07-162739-6, 978-1-07-162740-2
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Authors |
Morales-Sanchez, Abigail, Shissler, Susannah C, Cowan, Jennifer E, Bhandoola, Avinash, Shissler, Susannah C., Cowan, Jennifer E. |
Abstract |
Thymic epithelial cells (TECs) make up the thymic microenvironments that support the generation of a functionally competent and self-tolerant T-cell repertoire. Cortical (c)TECs, present in the cortex, are essential for early thymocyte development including selection of thymocytes expressing functional TCRs (positive selection). Medullary (m)TECs, located in the medulla, play a key role in late thymocyte development, including depletion of self-reactive T cells (negative selection) and selection of regulatory T cells. In recent years, transcriptomic analysis by single-cell (sc)RNA sequencing (Seq) has revealed TEC heterogeneity previously masked by population-level RNA-Seq or phenotypic studies. We summarize the discoveries made possible by scRNA-Seq, including the identification of novel mTEC subsets, advances in understanding mTEC promiscuous gene expression, and TEC alterations from embryonic to adult stages. Whereas pseudotime analyses of scRNA-Seq data can suggest relationships between TEC subsets, experimental methods such as lineage tracing and reaggregate thymic organ culture (RTOC) are required to test these hypotheses. Lineage tracing - namely, of β5t or Aire expressing cells - has exposed progenitor and parent-daughter cellular relationships within TEC. |
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Immunology and Microbiology | 1 | 50% |
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