Dataset Information

Premature senescence and increased oxidative stress in the thymus of Down Syndrome patients

ABSTRACT: Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in down syndrome (DS) patients, normally seen in older healthy subjects. We then performed RNA-Seq analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased -galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. Overall design: RNA-Seq analysis on sorted CD45- Epcam-enriched hTEC from DS patients and HD. Frozen samples of 3 normal HD and 3 DS patients were analyzed, for a total of 12 samples (Epcam+ and Epcam- for each of the 6 patients).

INSTRUMENT(S): Illumina NextSeq 500 (Homo sapiens)

ORGANISM(S): Homo Sapiens

SUBMITTER: Stefano Beretta

PROVIDER: GSE167021 | GEO | 2021-12-24

REPOSITORIES: GEO

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			Action	DRS
	GSE167021_counts.tsv.gz	Tabular

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Publications

Premature Senescence and Increased Oxidative Stress in the Thymus of Down Syndrome Patients.

Marcovecchio Genni Enza GE Ferrua Francesca F Fontana Elena E Beretta Stefano S Genua Marco M Bortolomai Ileana I Conti Anastasia A Montin Davide D Cascarano Maria Teresa MT Bergante Sonia S D'Oria Veronica V Giamberti Alessandro A Amodio Donato D Cancrini Caterina C Carotti Adriano A Di Micco Raffaella R Merelli Ivan I Bosticardo Marita M Villa Anna A

Frontiers in immunology 20210601

Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues. Based on previous studies suggesting immune senescence in DS, we hypothesized that induction of cellular senescence may contribute to ea ...[more]

PMID: 34140950

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