Editorial: Thymus function and aging: A focus on thymic epithelial cells

Shichkin, Valentin P.; Felli, María Pía; Screpanti, Isabella; Antica, Mariastefania

doi:10.3389/fimmu.2022.1003490

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…They maintain T-cell development at different stages through positive and negative selection, so TECs are an indispensable component of T lymphocyte maturation in the thymus [ 3 , 4 ]. However, in humans and mice, the thymus begins to degenerate after birth, and the reticular structure of the thymus epithelium is gradually replaced by adipose tissue, accompanied by a decrease in T-cell output [ 5 , 6 ]. Some experiments have shown that TECs have lower proliferation potential and that there is a higher percentage of apoptotic and senescent TECs in elderly animals, indicating that these cells may be a potential target for thymus rejuvenation therapy [ [7] , [8] , [9] ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

Yang,

Tian,

et al. 2024

Regenerative Therapy

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

Yang,

Tian,

et al. 2024

Regenerative Therapy

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“…Thymic epithelial cells (TECs), the major constituent of thymic stromal cells, are crucial for the thymic milieu and all phases of T-cell maturation. The thymus is the principal immunological organ that produces both immune-competent and self-tolerant T cells [1][2][3]. Nonetheless, during the first several months of life, the thymus progressively atrophies, which causes an ongoing decrease in thymic cell structure and disruption of the thymic stromal milieu.…”

Section: Introductionmentioning

confidence: 99%

Whole-transcriptome profiling reveals potential biomarkers for the reversal of thymic epithelial cell senescence by umbilical cord mesenchymal stem cells

Yang,

Tian,

et al. 2024

Aging

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Background: Reduced numbers and dysfunction of thymic epithelial cells (TECs) are important factors of thymic degeneration. Previous studies have found that umbilical cord mesenchymal stem cells (UCMSCs) reverse the structure and function of the senescent thymus in vivo. However, the transcriptomic regulation mechanism is unclear. Methods: TECs were cultured with H2O2 for 72 hours to induce senescence. UCMSCs were cocultured with senescent TECs for 48 hours to detect SA-β-gal, P16 and Ki67. The cocultured TECs were collected for lncRNA, mRNA and miRNA sequencing to establish a competitive endogenous regulatory network (ceRNA). And RT-qPCR, immunofluorescence staining, and western blot were used to identified key genes. Results: Our results showed that H2O2 induced TEC aging and that UCMSCs reversed these changes. Compared with those in aged TECs, 2260 DE mRNAs, 1033 DE lncRNAs and 67 DE miRNAs were differentially expressed, and these changes were reversed by coculturing the cells with UCMSCs. Differential mRNA enrichment analysis of ceRNA regulation revealed that the PI3K-AKT pathway was a significant signaling pathway. UCMSC coculture upregulated VEGFA, which is the upstream factor of the PI3K-AKT signaling pathway, and the expression of the key proteins PI3K and AKT. Thus, the expression of the cell cycle suppressor P27, which is downstream of the PI3K-AKT signaling pathway, was downregulated, while the expression of the cell cycle regulators CDK2 and CCNE was upregulated. Conclusion: UCMSC coculture upregulated the expression of VEGFA, activated the PI3K-Akt signaling pathway, increased the expression of CDK2 and CCNE, decreased the expression of P27, and promoted the proliferation of TECs.

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Umbilical cord subtotipotent-like stem cells reverse the ageing of thymic epithelial cells by inducing reprogramming of the whole-genome methylation and transcription profile

Yang¹,

Zhu³

et al. 2022

Preprint

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Background: A decrease in the number and activity of thymic epithelial cells (TECs) is an important factor in thymic degeneration, which can lead to dysfunction of T-cell differentiation, development and selection and a decrease in human immune function. Umbilical cord pluripotent-like stem cells (UCSSCs) can promote the structural and functional regeneration of the ageing thymus in vivo, but the mechanism of their action on TECs and molecules is not clear. Based on the discovery that UCSSCs promote thymus regeneration, we further analysed the changes in genome methylation modification profiles and their association with transcription profiles in ageing TECs cocultured with UCSSCs. Results: UCSSCs could promote thymus regeneration in ageing macaque monkeys, and an ageing model of TECs was established. Coculture of ageing TECs with UCSSCs for 48 hours significantly reduced the expression levels of ageing markers such as P16, P21 and p53 and increased the activity of ageing TECs. Genome-wide methylation and transcriptional sequencing analysis of TECs showed that methylation levels of 501 genes increased and 591 genes decreased in the promoter region. Twenty-three genes with increased methylation were enriched in the processes of negative regulation of cell growth, proliferation and apoptosis, and 37 genes with decreased methylation were enriched in the processes of promoting cell growth and proliferation and inhibiting apoptosis. Association analysis between promoter and transcription level revealed that there was a significant negative correlation between promoter methylation level and gene transcription in 66 genes, among which PDE5A, DUOX2, LAMP1 and SVIL, which inhibit growth and development, showed increased methylation and decreased transcription. Decreased methylation of POLR3G, PGF, CHTF18, KRT17, FOXJ1, NGF, DYRK3, LRP8, CDT1, PRELID1, F2R, KNTC1 and TRIM3, which promote cell growth, leads to an increase in transcription levels. Decreased promoter methylation of the transcription factor NGF gene, which leads to an increase in KRT17 and FOXJ1 transcription, plays a key role in reversing TEC senescence. Conclusion: UCSSC coculture ameliorates the age-associated hallmarks of ageing TECs. The methylation profile of senescent TEC genes was significantly changed after treatment with umbilical cord pluripotent stem cells. It was found that decreasing the methylation level of the transcription factor NGF and increasing the expression level of KRT17 and FOXJ1 play a key role in promoting the proliferation of TECs.

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Editorial: Thymus function and aging: A focus on thymic epithelial cells

Cited by 3 publications

References 12 publications

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

Whole-transcriptome profiling reveals potential biomarkers for the reversal of thymic epithelial cell senescence by umbilical cord mesenchymal stem cells

Umbilical cord subtotipotent-like stem cells reverse the ageing of thymic epithelial cells by inducing reprogramming of the whole-genome methylation and transcription profile

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