Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, 60126, Ancona, Italy.
Department of Biotechnology, University of Verona, Strada le Grazie 15, 37134, Verona, Italy.
Stem Cell Rev Rep. 2021 Jun;17(3):1014-1026. doi: 10.1007/s12015-020-10095-6. Epub 2021 Jan 6.
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.
衰老是人类疾病发生的主要风险因素之一，确定衰老的特征仍然是为老年人开发适当治疗靶点的挑战。在这里，我们通过分析其 miRNA 谱比较了两种间充质基质细胞群体的衰老相关变化：人牙髓基质细胞（hDPSCs）和人骨膜衍生祖细胞（hPDPCs）。这些细胞收获后，进行总 RNA 提取和全基因组 miRNA 谱分析，并应用 DIANA-miRPath 分析寻找靶标/途径。只有 69 个 microRNAs 在牙髓和骨膜祖细胞之间表现出显著的差异表达。其中，与 hPDPCs 相比，hDPSCs 中有 24 个上调，45 个下调。我们的注意力集中在 miRNA（22 个上调和 34 个下调）上，这些 miRNA 参与细胞衰老（即 p53、mTOR 途径）、自噬（即 mTOR 和 MAPK 途径）和细胞周期（即 MAPK 途径）的常见途径。p53、mTOR 和 MAPK 信号通路分别包含 43、37 和 112 个被所有选定 miRNA 靶向的基因。我们的发现与胚胎起源影响细胞行为和衰老过程的观点一致。我们的研究支持这样一种假设，即衰老由许多通过复杂的分子网络相互作用的介质驱动，这影响了成人干细胞的自我更新能力。
