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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 27, 2024 |
| Title |
Age-related epithelial defects limit thymic function and regeneration [single cell; Foxn1Lin] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in non-hematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated (aa)TECs formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of non-productive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition (EMT), and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTEC drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTEC expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune boosting therapies in older individuals.
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| Overall design |
Single cell RNA-seq profiles of CD45- thymic cells from Foxn1 lineage trace and wild type 20-month-old mice at steady state.
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| Contributor(s) |
Kousa AI, Jahn L, Zhao K, Flores AE, Acenas II D, Lederer E, Argyropoulos KV, Lemarquis AL, Granadier D, Cooper K, D’Andrea M, Sheridan JM, Tsai J, Sikkema L, Lazrak A, Nichols K, Lee N, Ghale R, Malard F, Andrlova H, Velardi E, Youssef S, Burgos da Silva M, Docampo M, Sharma R, Mazutis L, Wimmer VC, Rogers KL, DeWolf S, Gipson B, Gomes AL, Setty M, Pe'er D, Hale L, Manley NR, Gray DH, van den Brink MR, Dudakov JA |
| Citation(s) |
39112630 |
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| Submission date |
Dec 08, 2023 |
| Last update date |
Sep 26, 2024 |
| Contact name |
Anastasia I Kousa |
| E-mail(s) |
akousa@coh.org
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| Organization name |
City of Hope
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| Department |
Hematology / HCT
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| Lab |
The Marcel van den Brink Lab
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| Street address |
1500 E Duarte Rd
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| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (3) |
| GSM7963646 |
20-mo CD45- thymic stoma cells - Foxn1Lin - female [singe cell] |
| GSM7963647 |
20-mo CD45- thymic stoma cells - Foxn1Lin - male [singe cell] |
| GSM7963648 |
20-mo CD45- thymic stoma cells - wild type - male [singe cell] |
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| This SubSeries is part of SuperSeries: |
| GSE240020 |
Age-related epithelial defects limit thymic function and regeneration |
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| Relations |
| BioProject |
PRJNA1050287 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE249753_CD45neg_thymic_stroma_Foxn1TdTom+annotation.h5ad |
637.6 Mb |
(ftp)(http) |
H5AD |
| GSE249753_CD45neg_thymic_stroma_Foxn1TdTom_TEC+annotation.h5ad |
441.4 Mb |
(ftp)(http) |
H5AD |
| GSE249753_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of CSV, H5, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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