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

点击翻译按钮获取中文摘要

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.