Scholarlink

<p>The thymus educates thymocytes through a selection process mediated by thymic epithelial cells (TECs). Recent advances have made the generation of T lymphocytes from induced pluripotent stem cells (iPSc) a promising therapeutic strategy. However, current approaches often fail to replicate the thymic niche, leading to impaired T cell generation. Here we address the production of functional mature iPSc-derived TECs supporting in vitro T cell generation. We optimize thymic lineage differentiation through an unbiased multifactorial experimental design. By modulating specific signaling pathways, we generate progenitors that mature into medullary and cortical TECs. Co-culture with primary hematopoietic progenitors in a 3D thymic organoid setup induces their differentiation into CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Importantly, thymic organoids support multilineage differentiation, with dendritic cell populations also emerging. Thus, the presented thymic organoid model provides a practical platform for studying thymic cellular interactions and thymopoiesis in vitro, and opens further research perspectives towards cell-based therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Combinatory differentiation of human induced pluripotent stem cells generates functional thymic epithelium driving dendritic cell and CD4/CD8 T cell development

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月23日

查看全文
  • Nathan Provin,
  • Manon d’Arco,
  • Antoine Le Bozec,
  • Erwan Kervagoret,
  • Alexandre Bruneau,
  • Lucas Brusselle,
  • Cynthia Fourgeux,
  • Jeremie Poschmann,
  • Philippe Hulin,
  • Pierre Maminirina,
  • Olivier Baron,
  • Xavier Saulquin,
  • Carole Guillonneau,
  • Laurent David,
  • Matthieu Giraud

摘要

The thymus educates thymocytes through a selection process mediated by thymic epithelial cells (TECs). Recent advances have made the generation of T lymphocytes from induced pluripotent stem cells (iPSc) a promising therapeutic strategy. However, current approaches often fail to replicate the thymic niche, leading to impaired T cell generation. Here we address the production of functional mature iPSc-derived TECs supporting in vitro T cell generation. We optimize thymic lineage differentiation through an unbiased multifactorial experimental design. By modulating specific signaling pathways, we generate progenitors that mature into medullary and cortical TECs. Co-culture with primary hematopoietic progenitors in a 3D thymic organoid setup induces their differentiation into CD4+ and CD8+ T cells. Importantly, thymic organoids support multilineage differentiation, with dendritic cell populations also emerging. Thus, the presented thymic organoid model provides a practical platform for studying thymic cellular interactions and thymopoiesis in vitro, and opens further research perspectives towards cell-based therapies.