The Francis Crick Institute
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Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus

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journal contribution
posted on 2023-11-23, 11:28 authored by Roberta Ragazzini, Stefan Boeing, Luca Zanieri, Mary Green, Giuseppe D’Agostino, Kerol Bartolovic, Ana Agua-Doce, Maria Greco, Sara A Watson, Antoniana Batsivari, Linda Ariza-McNaughton, Asllan Gjinovci, David Scoville, Andy Nam, Adrian C Hayday, Dominique Bonnet, Paola Bonfanti
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.


Crick (Grant ID: CC2027, Grant title: Bonnet CC2027) Crick (Grant ID: CC2012, Grant title: Hayday CC2012) Crick (Grant ID: CC1107, Grant title: STP Bioinformatics & Biostatistics) Crick (Grant ID: CC1061, Grant title: STP Experimental Histopathology) Crick (Grant ID: CC1062, Grant title: STP Flow Cytometry)