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<p>The human thymus plays a key role in the development of the adaptive immune system. Its development and pathologic aberrations with missing involution occupy the scientific world for years. Here, we present a comprehensive single-cell RNA sequencing (scRNA-seq) analysis of 453,727 cells across 53 datasets derived from healthy prenatal, pediatric, and adult thymic tissues, as well as six pathological conditions, including thymic hyperplasia and thymic epithelial tumors (types A, AB, B, C, and micronodular thymoma). We created a high-resolution cellular atlas revealing disease-specific cellular populations and transcriptional programs, particularly within fibroblast subsets and thymic epithelial cells. Comparative analysis uncovers distinct intercellular communication patterns and identifies transcriptional alterations associated with thymic pathology. Integration with published bulk RNA-seq datasets supports the robustness and translational relevance of our findings. This study provides a foundational resource for understanding the cellular and molecular landscape of thymic development and disease, offering avenues for diagnostic and therapeutic innovations.</p>

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A single-cell atlas revealing cellular heterogeneity across healthy and diseased human thymus

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月6日

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  • Martin Direder,
  • Matthias Wielscher,
  • Melanie Salek,
  • Maria Laggner,
  • Dragan Copic,
  • Katharina Klas,
  • Daniel Bormann,
  • Bahar Golabi,
  • Hannes Kühtreiber,
  • Marie-Therese Lingitz,
  • Leonhard Müllauer,
  • Ana-Iris Schiefer,
  • Wolfgang Weninger,
  • Clemens Aigner,
  • Hendrik Jan Ankersmit,
  • Michael Mildner,
  • Bernhard Moser

摘要

The human thymus plays a key role in the development of the adaptive immune system. Its development and pathologic aberrations with missing involution occupy the scientific world for years. Here, we present a comprehensive single-cell RNA sequencing (scRNA-seq) analysis of 453,727 cells across 53 datasets derived from healthy prenatal, pediatric, and adult thymic tissues, as well as six pathological conditions, including thymic hyperplasia and thymic epithelial tumors (types A, AB, B, C, and micronodular thymoma). We created a high-resolution cellular atlas revealing disease-specific cellular populations and transcriptional programs, particularly within fibroblast subsets and thymic epithelial cells. Comparative analysis uncovers distinct intercellular communication patterns and identifies transcriptional alterations associated with thymic pathology. Integration with published bulk RNA-seq datasets supports the robustness and translational relevance of our findings. This study provides a foundational resource for understanding the cellular and molecular landscape of thymic development and disease, offering avenues for diagnostic and therapeutic innovations.