Ragazzini, Roberta;
Boeing, Stefan;
Zanieri, Luca;
Green, Mary;
D'Agostino, Giuseppe;
Bartolovic, Kerol;
Agua-Doce, Ana;
... Bonfanti, Paola; + view all
(2023)
Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus.
Developmental Cell
10.1016/j.devcel.2023.08.017.
(In press).
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2023.08.017 |
| Publisher version: | https://doi.org/10.1016/j.devcel.2023.08.017 |
| Language: | English |
| Additional information: | © 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | 3D imaging, BCAM, epithelial stem cells, human thymus, in vitro self-renewal, multipotency, single-cell clonal assay, spatial phenotyping, spatial transcriptomics, stem cell niche |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10176279 |
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