Age-related transcriptional modules and TF-miRNA-mRNA interactions in neonatal and infant human thymus

PLoS One. 2020 Apr 15;15(4):e0227547. doi: 10.1371/journal.pone.0227547. eCollection 2020.

Abstract

The human thymus suffers a transient neonatal involution, recovers and then starts a process of decline between the 1st and 2nd years of life. Age-related morphological changes in thymus were extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Through Weighted Gene Co-expression Network Analysis (WGCNA) and TF-miRNA-mRNA integrative analysis we studied the transcriptome of neonate and infant thymic tissues grouped by age: 0-30 days (A); 31days-6 months (B); 7-12 months (C); 13-18 months (D); 19-31months (E). Age-related transcriptional modules, hubs and high gene significance (HGS) genes were identified, as well as TF-miRNA-hub/HGS co-expression correlations. Three transcriptional modules were correlated with A and/or E groups. Hubs were mostly related to cellular/metabolic processes; few were differentially expressed (DE) or related to T-cell development. Inversely, HGS genes in groups A and E were mostly DE. In A (neonate) one third of the hyper-expressed HGS genes were related to T-cell development, against one-twentieth in E, what may correlate with the early neonatal depletion and recovery of thymic T-cell populations. This genomic mechanism is tightly regulated by TF-miRNA-hub/HGS interactions that differentially govern cellular and molecular processes involved in the functioning of the neonate thymus and in the beginning of thymic decline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Cell Differentiation / genetics
  • Child, Preschool
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Regulatory Networks*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sex Factors
  • T-Lymphocytes / physiology*
  • Thymus Gland / growth & development*
  • Thymus Gland / surgery
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • MicroRNAs
  • RNA, Messenger
  • Transcription Factors

Grants and funding

The work was funded by grants awarded to VHH from FRAM - High North Research Centre for Climate and the Environment through the Flagship MIKON (Project RConnected; https://www.framcentre.com/) and the Arctic Belmont Forum Arctic Observing and Research for Sustainability (Project CONNECT; https://www.belmontforum.org/). The Norwegian collaboration was financed by Norwegian Research Council grant 247474 (https://www.forskningsradet.no/en). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.