Qi Huilin, Aguiar Dean J, Williams Shelly M, La Pean Alison, Pan Wei, Verfaillie Catherine M
Stem Cell Institute, Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55445, USA.
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3305-10. doi: 10.1073/pnas.0532693100. Epub 2003 Mar 11.
Single human bone marrow-derived mesodermal progenitor cells (MPCs) differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, and endothelial cells. To identify genes involved in the commitment of MPCs to osteoblasts we examined the expressed gene profile of undifferentiated MPCs and MPCs induced to the osteoblast lineage for 1-7 days by cDNA microarray analysis. As expected, growth factor, hormone, and signaling pathway genes known to be involved in osteogenesis were activated during differentiation. In addition, 41 transcription factors (TFs) were differentially expressed over time, including TFs with known roles in osteoblast differentiation and TFs not known to be involved in osteoblast differentiation. As the latter group of TFs coclustered with osteogenesis-specific TFs, they may play a role in osteoblast differentiation. When we compared the gene expression profile of MPCs induced to differentiate to chondroblasts and osteoblasts, significant differences in the nature and/or timing of gene activation were seen. These studies indicate that in vitro differentiation cultures in which MPCs are induced to one of multiple cell fates should be very useful for defining signals important for lineage-specific differentiation.
单个源自人骨髓的中胚层祖细胞(MPCs)可分化为成骨细胞、软骨细胞、脂肪细胞、肌细胞和内皮细胞。为了鉴定参与MPCs向成骨细胞定向分化的基因,我们通过cDNA微阵列分析检测了未分化的MPCs以及诱导至成骨细胞谱系1 - 7天的MPCs的基因表达谱。正如预期的那样,已知参与骨生成的生长因子、激素和信号通路基因在分化过程中被激活。此外,41种转录因子(TFs)随时间差异表达,包括在成骨细胞分化中具有已知作用的TFs以及未知参与成骨细胞分化的TFs。由于后一组TFs与骨生成特异性TFs共聚类,它们可能在成骨细胞分化中发挥作用。当我们比较诱导分化为软骨细胞和成骨细胞的MPCs的基因表达谱时,发现基因激活的性质和/或时间存在显著差异。这些研究表明,在体外分化培养中,将MPCs诱导为多种细胞命运之一对于确定谱系特异性分化的重要信号应该非常有用。