MicroRNA Profiling in Mesenchymal Stromal Cells: the Tissue Source as the Missing Piece in the Puzzle of Ageing

Abstract

Ageing is among the main risk factors for human disease onset and the identification of the hallmarks of senescence remains a challenge for the development of appropriate therapeutic target in the elderly. Here, we compare senescence-related changes in two cell populations of mesenchymal stromal cells by analysing their miRNA profiling: Human Dental Pulp Stromal Cells (hDPSCs) and human Periosteum-Derived Progenitor Cells (hPDPCs). After these cells were harvested, total RNA extraction and whole genome miRNA profiling was performed, and DIANA-miRPath analysis was applied to find the target/pathways. Only 69 microRNAs showed a significant differential expression between dental pulp and periosteum progenitor cells. Among these, 24 were up regulated, and 45 were downregulated in hDPSCs compared to hPDPCs. Our attention was centered on miRNAs (22 upregulated and 34 downregulated) involved in common pathways for cell senescence (i.e. p53, mTOR pathways), autophagy (i.e. mTOR and MAPK pathways) and cell cycle (i.e. MAPK pathway). The p53, mTOR and MAPK signaling pathways comprised 43, 37 and 112 genes targeted by all selected miRNAs, respectively. Our finding is consistent with the idea that the embryological origin influences cell behavior and the ageing process. Our study strengthens the hypothesis that ageing is driven by numerous mediators interacting through an intricate molecular network, which affects adult stem cells self-renewal capability. Graphical abstract.

Keywords: Ageing; Autophagy; Cell cycle; Dental pulp stem cells (DPSCs); Periosteum-derived progenitor cells (PDPCs); Senescence; microRNAs.