Istituto di Ricerca Genetica e Biomedica (IRGB), del Consiglio Nazionale delle Ricerche (CNR), Cittadella Universitaria di Cagliari, S.S. 554 bivio per Sestu, 09042, Monserrato, CA, Italy.
Mol Biol Rep. 2012 Apr;39(4):3995-4007. doi: 10.1007/s11033-011-1180-9. Epub 2011 Jul 20.
The adult bone marrow contains a subset of non-haematopoietic cells referred to as bone marrow mesenchymal stem cells (BMSCs). Mesenchymal stem cells (MSCs) have attracted immense research interest in the field of regenerative medicine due to their ability to be cultured for successive passages and multi-lineage differentiation. The molecular mechanisms governing the self-renewal and differentiation of MSCs remain largely unknown. In a previous paper we demonstrated the ability to induce human clonal MSCs to differentiate into cells with a neuronal phenotype (DMSCs). In the present study we evaluated gene expression profiles by Sequential Analysis of Gene Expression (SAGE) and microRNA expression profiles before and after the neuronal differentiation process. Various tissue-specific genes were weakly expressed in MSCs, including those of non-mesodermal origin, suggesting multiple potential tissue-specific differentiation, as well as stemness markers. Expression of OCT4, KLF4 and c-Myc cell reprogramming factors, which are modulated during the differentiation process, was also observed. Many peculiar nervous tissue genes were expressed at a high level in DMSCs, along with genes related to apoptosis. MicroRNA profiling and correlation with mRNA expression profiles allowed us to identify putative important genes and microRNAs involved in the differentiation of MSCs into neuronal-like cells. The profound difference in gene and microRNA expression patterns between MSCs and DMSCs indicates a real functional change during differentiation from MSCs to DMSCs.
成人骨髓中含有一小部分非造血细胞，称为骨髓间充质干细胞（BMSCs）。间充质干细胞（MSCs）因其能够进行连续传代和多谱系分化而在再生医学领域引起了极大的研究兴趣。调节 MSC 自我更新和分化的分子机制在很大程度上尚不清楚。在之前的一篇论文中，我们证明了诱导人克隆 MSC 分化为具有神经元表型的细胞（DMSCs）的能力。在本研究中，我们通过基因表达序列分析（SAGE）和神经元分化前后的 microRNA 表达谱评估了基因表达谱。在 MSCs 中，各种组织特异性基因表达较弱，包括非中胚层来源的基因，这表明具有多种潜在的组织特异性分化以及干性标志物。还观察到细胞重编程因子 OCT4、KLF4 和 c-Myc 的表达，这些因子在分化过程中受到调节。许多特有的神经组织基因在 DMSCs 中高水平表达，同时也与凋亡相关基因相关。microRNA 分析及其与 mRNA 表达谱的相关性使我们能够鉴定出参与 MSC 向神经元样细胞分化的潜在重要基因和 microRNAs。MSC 和 DMSCs 之间基因和 microRNA 表达模式的巨大差异表明，在从 MSC 向 DMSCs 分化过程中确实发生了功能变化。
