The human thymus shows a transient involution along the neonatal period and starts a continuous process of decline between the 1st and 2nd years. The immune alterations associated to thymic aging in humans have been extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Here we conducted a temporal gene co-expression network analysis in the newborn and infant thymic tissue aiming to identify transcriptional modules associated to age.
Whole transcriptional profiles of newborn and infant thymus surgical explants (31 males and 23 females) grouped by age intervals – 0-30d (A), 31d-6mo (B), 7-12mo (C), 13-18mo (D), and 19-31mo (E) - were analyzed using the Weighted Gene Co-expression Networks Analysis (WGCNA). The genomic analyses were centered in: i) identification of transcriptional modules; ii) node categorization (hubs, HGS genes); iii) integrative mRNA-miRNA-transcription factors (TFs) co-expression networks.
Three transcriptional modules were correlated with A (neonate) and/or E groups. The two modules positively correlated with the E group (mean age 25 months) harbor comparatively more hubs related to T-cell and thymic stromal functions. Interestingly, most of the HGS genes hyper-expressed in group A (A vs E comparison) are involved in T-cell development and stromal functions. Integrative network analysis revealed that HGS genes have more links with miRNAs and TFs when compared with hubs.
Our results show that hubs are related to network/module robustness. Conversely, the differentially expressed HGS genes, acting as bridges between modules or as border genes, may well be markers of age-related thymic processes.
FAPESP 2014/50489-9; 2015/22308-2