Defining the Identity and the Niches of Epithelial Stem Cells with Highly Pleiotropic Multilineage Potency in the Human Thymus

Overview

Journal Dev Cell

Publisher Cell Press

Specialties Cell Biology
Reproductive Medicine

Date 2023 Aug 31

PMID 37652013

Authors

Roberta Ragazzini

Stefan Boeing

Luca Zanieri

Mary Green

Giuseppe DAgostino

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

Affiliations

Soon will be listed here.

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.

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