Ageing compromises mouse thymus function and remodels epithelial cell differentiation.

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

Elife

journal_title

eLife

authors

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 GA

doi

10.7554/eLife.56221

subject

Has Abstract

pub_date

2020-08-25 00:00:00

issn

2050-084X

pii

56221

journal_volume

9

pub_type

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