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| Status |
Public on May 23, 2015 |
| Title |
Age associated differences in miRNA signatures are restricted to CD45RO negative T cells and are associated with changes in the cellular composition, activation and cellular ageing |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
MicroRNAs (miRNAs) have emerged as important players in the regulation of T-cell functionality. However, comprehensive insight into the extent of age-related miRNA changes in T cells is lacking. We established miRNA expression patterns of CD45RO- naïve and CD45RO+ memory T-cell subsets isolated from peripheral blood cells from young and elderly individuals. Unsupervised clustering of the miRNA expression data revealed an age-related clustering in the CD45RO- T cells, while CD45RO+ T cells clustered based on expression of CD4 and CD8. Seventeen miRNAs showed an at least 2-fold up- or downregulation in CD45RO- T cells obtained from young as compared to old donors. Validation on the same and independent samples revealed a statistically significant age-related upregulation of miR-21, miR-223 and miR-15a. In a T-cell subset analysis focusing on known age-related phenotypic changes, we showed significantly higher miR-21 and miR-223 levels in CD8+CD45RO-CCR7- TEMRA compared to CD45RO-CCR7+ TNAIVE-cells. Moreover, miR-21 but not miR-223 levels were significantly increased in CD45RO-CD31- post-thymic TNAIVE cells as compared to thymic CD45RO-CD31+ TNAIVE cells. Upon activation of CD45RO- TNAIVE cells we observed a significant induction of miR-21 especially in CD4+ T cells, while miR-223 levels significantly decreased only in CD4+ T cells. Besides composition and activation, we showed a borderline significant increase in miR-21 levels upon an increasing number of population doublings in CD4+ T-cell clones. Together, our results show that ageing related changes in miRNA expression are dominant in the CD45RO- T-cell compartment. The differential expression patterns can be explained by age related changes in T-cell composition, i.e. accumulation of CD8+ TEMRA and CD4+ post thymic expanded CD31- T cells and by cellular ageing, as demonstrated in a longitudinal clonal culture model.
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| Overall design |
MicroRNA profiling was performed in eight T cell subsets: CD4 naive (CD3+CD4+CD45RO-), CD8 naive (CD3+CD4-CD45RO-), CD4 memory (CD3+CD4+CD45RO+) and CD8 memory (CD3+CD4-CD45RO+) T cells derived from 5 healthy young and 5 healthy old participants.
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| Contributor(s) |
Teteloshvili N, Kluiver J, van der Geest KS, van der Lei RJ, Jellema P, Pawelec G, Brouwer E, Kroesen BJ, Boots AM, van den Berg A |
| Citation(s) |
26360056 |
| Submission date |
May 22, 2015 |
| Last update date |
Dec 09, 2015 |
| Contact name |
Anke van den Berg |
| E-mail(s) |
a.van.den.berg01@umcg.nl
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| Phone |
+31503611476
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| Organization name |
University Medical Center Groningen
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| Department |
Department of Pathology and Medical Biology
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| Street address |
Hanzeplein 1
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| City |
Groningen |
| ZIP/Postal code |
9700RB |
| Country |
Netherlands |
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| Platforms (1) |
| GPL8227 |
Agilent-019118 Human miRNA Microarray 2.0 G4470B (miRNA ID version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA284773 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE69191_RAW.tar |
6.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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