Brunelli Silvia, Tagliafico Enrico, De Angelis Fernanda G, Tonlorenzi Rossana, Baesso Silvia, Ferrari Sergio, Niinobe Michio, Yoshikawa Kazuaki, Schwartz Robert J, Bozzoni Irene, Ferrari Stefano, Cossu Giulio
Stem Cell Research Institute, DIBIT-H, Milan, Italy.
Circ Res. 2004 Jun 25;94(12):1571-8. doi: 10.1161/01.RES.0000132747.12860.10. Epub 2004 May 20.
Little is known about the molecular mechanism underlying specification and differentiation of smooth muscle (SM), and this is, at least in part, because of the few cellular systems available to study the acquisition of a SM phenotype in vitro. Mesoangioblasts are vessel-derived stem cells that can be induced to differentiate into different cell types of the mesoderm, including SM. We performed a DNA microarray analysis of a mesoangioblast clone that spontaneously expresses an immature SM phenotype and compared it with a sister clone mainly composed of undifferentiated progenitor cells. This study allowed us to define a gene expression profile for "stem" cells versus smooth muscle cells (SMCs) in the absence of differentiation inducers such as transforming growth factor beta. Two transcription factors, msx2 and necdin, are expressed at least 100 times more in SMCs than in stem cells, are coexpressed in all SMCs and tissues, are induced by transforming growth factor beta, and, when coexpressed, induce a number of SM markers in mesoangioblast, fibroblast, and endothelial cell lines. Conversely, their downregulation through RNA interference results in a decreased expression of SM markers. These data support the hypothesis that Msx2 and necdin act as master genes regulating SM differentiation in at least a subset of SMCs.
关于平滑肌(SM)特化和分化的分子机制,我们了解甚少,这至少部分是由于体外研究SM表型获得的细胞系统较少。中胚层血管母细胞是源自血管的干细胞,可被诱导分化为中胚层的不同细胞类型,包括SM。我们对一个自发表达未成熟SM表型的中胚层血管母细胞克隆进行了DNA微阵列分析,并将其与一个主要由未分化祖细胞组成的姐妹克隆进行了比较。这项研究使我们能够在没有诸如转化生长因子β等分化诱导剂的情况下,确定“干”细胞与平滑肌细胞(SMC)的基因表达谱。两种转录因子,msx2和necdin,在SMC中的表达至少比在干细胞中高100倍,在所有SMC和组织中共同表达,由转化生长因子β诱导,并且共同表达时,可在中胚层血管母细胞、成纤维细胞和内皮细胞系中诱导多种SM标志物。相反,通过RNA干扰下调它们会导致SM标志物的表达降低。这些数据支持这样的假设,即Msx2和necdin作为主基因,至少在一部分SMC中调节SM分化。