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<p>Cellular interactions between thymocytes and other immune and stromal thymic cells play a key role in T cell maturation and homeostasis. Previous efforts delineating the cellular interactomes that support T cell development have mostly relied on imaging techniques, genetic deletion of essential molecular factors and bone marrow chimeras. Here, using synthetic NOTCH receptors we took a direct and unbiased genetic approach to fluorescently label cells in physical contact with CD4<sup>+</sup> and CD4<sup>+</sup>CD8<sup>+</sup> thymocytes in vivo in mice. Prospective isolation and transcriptional characterization at single-cell level of the interacting cells exposed the thymic cellular interactome that supports these T cells and how ageing erodes these interactions. Cellular interactors included, among others, dendritic cells, B cells, IL-17<sup>+</sup> γδ T cells, fibroblast subsets and thymic epithelial cells. Ligand-receptor pair analyses highlighted signals involved in survival, differentiation and antigen presentation. Our work provides a new means to study thymic cellular interactions.</p>

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Unbiased recording and identification of thymic cellular interactomes using synthetic Notch receptors

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月9日

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  • Raúl Sánchez-Lanzas,
  • Amanda Jiménez-Pompa,
  • Elise Smith,
  • Nital Sumaria,
  • Justin Barclay,
  • Foteini Kalampalika,
  • Daniel J. Pennington,
  • Mirjana Efremova,
  • Miguel Ganuza

摘要

Cellular interactions between thymocytes and other immune and stromal thymic cells play a key role in T cell maturation and homeostasis. Previous efforts delineating the cellular interactomes that support T cell development have mostly relied on imaging techniques, genetic deletion of essential molecular factors and bone marrow chimeras. Here, using synthetic NOTCH receptors we took a direct and unbiased genetic approach to fluorescently label cells in physical contact with CD4+ and CD4+CD8+ thymocytes in vivo in mice. Prospective isolation and transcriptional characterization at single-cell level of the interacting cells exposed the thymic cellular interactome that supports these T cells and how ageing erodes these interactions. Cellular interactors included, among others, dendritic cells, B cells, IL-17+ γδ T cells, fibroblast subsets and thymic epithelial cells. Ligand-receptor pair analyses highlighted signals involved in survival, differentiation and antigen presentation. Our work provides a new means to study thymic cellular interactions.