Analysis of gene networks that regulate the differentiation program of mesenchymal stem cells

间充质干细胞（MSC）具有多能性、干细胞性和自我更新能力。MSC可以分化成各种类型的细胞，包括成骨细胞、软骨细胞和脂肪细胞。为了鉴定负责MSC特征的基因，我们对未分化和分化的MSC和对照成纤维细胞进行了DNA微阵列分析，并鉴定了180个在未分化MSC中特异性表达的基因。RT-PCR分析证实了180个基因中30个基因的特异性表达。由于这些包括9个转录因子基因，我们将它们的siRNA转染到MSC中。这些siRNA中的一些抑制MSC的生长，并且抑制或加速成骨分化的MSC。此外，使用来自胫骨、股骨、髂骨和颌骨的许多MSC系以及皮肤和牙龈成纤维细胞，我们鉴定了分子标记物-LIF、IGFI、PRGI、MGP、BMP 4、CTGF、KCTD 12、IGFBP7、TRIB 2和DYNC III-这些分子标记物在这些MSC中的表达水平高于成纤维细胞。传代数显著改变了几种标记物的表达水平，而供体年龄对其影响不大。虽然它们的功效可能取决于传代次数或供体年龄，但这些在各种MSC中常见的标记物可能在常规测试中有用。这些结果表明，这些转录因子和标记物中的一些是必需的MSC的分化和MSC的性质的维持。

Mesenchymal stem cells (MSC) are characterized by multipotency, sternness, and self-renewal. MSC can be differentiated into various types of cells including osteoblasts, chondrocytes, and adipocytes. To identify the genes responsible for the characteristics of MSC, we performed DNA microarray analysis for undifferentiated and differentiated MSC and control fibroblasts and identified 180 genes expressed specifically in undifferentiated MSC. The specific expression of 30 genes out of 180 genes was confirmed by RT-PCR analysis. Since these include 9 genes for transcription factors, we transfected their siRNAs into MSC. Some of these siRNAs inhibited growth of MSC, and inhibited or accelerated osteogenic differentiated MSC. Furthermore, using numerous MSC lines from tibia, femur, ilium, and jaw, together with skin and gum fibroblasts, we identified molecular markers - LIF, IGFI, PRGI, MGP, BMP4, CTGF, KCTD12, IGFBP7, TRIB2, and DYNCIII - that were expressed at a higher level in these MSCs than in fibroblasts. The passage number markedly altered the expression levels of several markers, while donor age had little effect on them. Although their efficacy may depend upon the passage number or donor age, these markers common among various MSCs are probably useful in routine tests. These results suggest that some of these transcription factors and markers are essential for differentiation of MSC and maintenance of the properties of MSC.