Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells

Identification of genes responsible for osteoblast differentiation from human mesodermal progenitor cells
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DOI:
10.1073/pnas.0532693100
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发表时间:
2003-03-18
影响因子:
11.1
通讯作者:
Verfaillie, CM
Verfaillie, CM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Qi, HL;Aguiar, DJ;Verfaillie, CM

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单个人骨髓来源的中胚层祖细胞(MPC)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MPC向成骨细胞定向的基因,我们通过cDNA微阵列分析检测了未分化MPC和诱导成骨细胞谱系1-7天的MPC的表达基因谱。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个转录因子(TF)随着时间的推移差异表达,包括已知在成骨细胞分化中的作用的TF和未知参与成骨细胞分化的TF。由于后一组TF与成骨特异性TF共簇,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成软骨细胞和成骨细胞的MPC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,MPC被诱导为多种细胞命运之一,这对于确定谱系特异性分化的重要信号是非常有用的。
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.