Ageing compromises mouse thymus function and remodels epithelial cell differentiation
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...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
eLife Sciences Publications
2020
|
| _version_ | 1826298644186267648 |
|---|---|
| author | 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 Hollander, G |
| author_facet | 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 Hollander, G |
| author_sort | Baran-Gale, J |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:50:02Z |
| format | Journal article |
| id | oxford-uuid:d49a4135-0495-485f-a3cd-c3194a36ad81 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:50:02Z |
| publishDate | 2020 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:d49a4135-0495-485f-a3cd-c3194a36ad812022-03-27T08:20:17ZAgeing compromises mouse thymus function and remodels epithelial cell differentiationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d49a4135-0495-485f-a3cd-c3194a36ad81EnglishSymplectic ElementseLife Sciences Publications2020Baran-Gale, JMorgan, MD Maio, SDhalla, FCalvo-Asensio, IDeadman, MEHandel, AEMaynard, AChen, SGreen, FSit, RV Neff, NFDarmanis, STan, WMay, APMarioni, JCPonting, CPHollander, GAgeing 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. |
| spellingShingle | 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 Hollander, G Ageing compromises mouse thymus function and remodels epithelial cell differentiation |
| title | Ageing compromises mouse thymus function and remodels epithelial cell differentiation |
| title_full | Ageing compromises mouse thymus function and remodels epithelial cell differentiation |
| title_fullStr | Ageing compromises mouse thymus function and remodels epithelial cell differentiation |
| title_full_unstemmed | Ageing compromises mouse thymus function and remodels epithelial cell differentiation |
| title_short | Ageing compromises mouse thymus function and remodels epithelial cell differentiation |
| title_sort | ageing compromises mouse thymus function and remodels epithelial cell differentiation |
| work_keys_str_mv | AT barangalej ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT morganmd ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT maios ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT dhallaf ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT calvoasensioi ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT deadmanme ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT handelae ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT maynarda ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT chens ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT greenf ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT sitrv ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT neffnf ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT darmaniss ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT tanw ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT mayap ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT marionijc ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT pontingcp ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation AT hollanderg ageingcompromisesmousethymusfunctionandremodelsepithelialcelldifferentiation |