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Updated: Jul 17, 2025

Author Spotlight: Advancing Thymic Epithelial Cells and T-Cell Research with Human Thymic Organoids
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Author Spotlight: Advancing Thymic Epithelial Cells and T-Cell Research with Human Thymic Organoids

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Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the

Roberta Ragazzini1, Stefan Boeing2, Luca Zanieri1

  • 1Epithelial Stem Cell Biology & Regenerative Medicine Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Institute of Immunity & Transplantation, Division of Infection & Immunity, UCL, Pears Building, Rosslyn Hill, London NW3 2PP, UK.

Developmental Cell
|August 31, 2023
PubMed

Thymus is necessary for lifelong immunological tolerance and immunity. It displays a distinctive epithelial complexity and undergoes age-dependent atrophy. Nonetheless, it also retains regenerative capacity, which, if harnessed appropriately, might permit rejuvenation of adaptive immunity. By characterizing cortical and medullary compartments in the human thymus at single-cell resolution, in this study we have defined specific epithelial populations, including those that share properties with bona fide stem cells (SCs) of lifelong regenerating epidermis. Thymic epithelial SCs display a distinctive transcriptional profile and phenotypic traits, including pleiotropic multilineage potency, to give rise to several cell types that were not previously considered to have shared origin. Using here identified SC markers, we have defined their cortical and medullary niches and shown that, in vitro, the cells display long-term clonal expansion and self-organizing capacity. These data substantively broaden our knowledge of SC biology and set a stage for tackling thymic atrophy and related disorders.

Keywords:
3D imagingBCAMepithelial stem cellshuman thymusin vitro self-renewalmultipotencysingle-cell clonal assayspatial phenotypingspatial transcriptomicsstem cell niche

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