Abstract:
:Ageing is characterised by cellular senescence, leading to imbalanced tissue maintenance, cell death and compromised organ function. This is first observed in the thymus, the primary lymphoid organ that generates and selects T cells. However, the molecular and cellular mechanisms underpinning these ageing processes remain unclear. Here, we show that mouse ageing leads to less efficient T cell selection, decreased self-antigen representation and increased T cell receptor repertoire diversity. Using a combination of single-cell RNA-seq and lineage-tracing, we find that progenitor cells are the principal targets of ageing, whereas the function of individual mature thymic epithelial cells is compromised only modestly. Specifically, an early-life precursor cell population, retained in the mouse cortex postnatally, is virtually extinguished at puberty. Concomitantly, a medullary precursor cell quiesces, thereby impairing maintenance of the medullary epithelium. Thus, ageing disrupts thymic progenitor differentiation and impairs the core immunological functions of the thymus.
journal_name
Elifejournal_title
eLifeauthors
Baran-Gale J,Morgan MD,Maio S,Dhalla F,Calvo-Asensio I,Deadman ME,Handel AE,Maynard A,Chen S,Green F,Sit RV,Neff NF,Darmanis S,Tan W,May AP,Marioni JC,Ponting CP,Holländer GAdoi
10.7554/eLife.56221subject
Has Abstractpub_date
2020-08-25 00:00:00issn
2050-084Xpii
56221journal_volume
9pub_type
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