Akavia Uri David, Veinblat Olga, Benayahu Dafna
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
J Cell Physiol. 2008 Sep;216(3):663-72. doi: 10.1002/jcp.21442.
Marrow-derived stroma cells (MSCs) can differentiate into multiple lineages including myogenic cells. However, the molecular mechanisms that direct MSCs to each differentiation pathway are poorly understood. Our study was designed to gain insights into the potential regulatory pathways that may assist in defining MSC commitment and differentiation properties. This will delineate the similarities or differences in the expression of genes between several cell types of mesenchymal origin. In this study, we established in vitro models, which allow following the discrete stages of differentiation of cardio- and myogenic-cells compared with MSC. Gene expression of each cell type at several stages of their differentiation path was evaluated by means of Affymetrix Gene Chips. Bioinformatic clustering of genes confirmed that with time in culture the myogenic cells ceased proliferating and commenced with differentiation. The expression profile analysis revealed the similarity and differences between myogenic cells and MSCs. This research compared at the molecular levels snapshots of gene expression patterns and elaborated on the overlap or differences between the analyzed cellular systems. Our results shed light on gene profiles of cells throughout their differentiation pathways. Establishing the gene signature of the differentiation process of cells that belong to several mesenchymal lineages may contribute to the understanding of molecular pathways that underlay mesenchymal tissue remodeling.
骨髓来源的基质细胞(MSCs)可分化为包括肌原性细胞在内的多种谱系。然而,指导MSCs进入各分化途径的分子机制却鲜为人知。我们的研究旨在深入了解可能有助于明确MSCs定向和分化特性的潜在调控途径。这将描绘间充质起源的几种细胞类型之间基因表达的异同。在本研究中,我们建立了体外模型,与MSCs相比,该模型能够追踪心肌细胞和肌原性细胞分化的离散阶段。利用Affymetrix基因芯片评估了每种细胞类型在其分化路径的几个阶段的基因表达。基因的生物信息聚类证实,随着培养时间的推移,肌原性细胞停止增殖并开始分化。表达谱分析揭示了肌原性细胞与MSCs之间的异同。本研究在分子水平上比较了基因表达模式的瞬间图像,并阐述了所分析的细胞系统之间的重叠或差异。我们的结果揭示了细胞在其整个分化途径中的基因谱。确定属于几种间充质谱系的细胞分化过程的基因特征可能有助于理解间充质组织重塑的分子途径。