PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs):: transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages
PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs):: transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages
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DOI：
10.1182/blood-2007-07-103697
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发表时间：
2008-07-15
期刊：
影响因子：
20.3
通讯作者：
Tanavde, Vivek
中科院分区：
文献类型：
--
作者：
Ng, Felicia;Boucher, Shayne;Tanavde, Vivek
我们比较了骨髓间充质干细胞（MSCs）的转录组与分化的脂肪细胞，骨细胞和软骨细胞来源于这些MSCs。使用全球基因表达谱阵列检测RNA转录本，我们已经确定了标记，是特定的骨髓间充质干细胞及其分化的后代。此外，我们还确定了MSC用于分化成脂肪形成、软骨形成和成骨谱系的途径。我们确定激活素介导的转化生长因子（TGF）-β信号传导，血小板衍生生长因子（PDGF）信号传导和成纤维细胞生长因子（FGF）信号传导是参与MSC分化的关键途径。当这些途径受到细胞表面受体功能抑制剂的干扰时，MSC分化成这些谱系受到影响。由于生长和分化是紧密相连的过程，我们还研究了这3种途径在MSC生长中的重要性。这3条途径是MSC生长所必需和充分的。抑制这些途径中的任何一种都会减缓MSC的生长，而TGF-β、PDGF和β-FGF的组合足以使MSC在无血清培养基中生长多达5代。因此，这项研究表明，使用微阵列数据预测细胞分化和生长中活跃的信号通路并通过实验验证这些预测是可能的。
We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs) with differentiated adipocytes, osteocytes, and chondrocytes derived from these MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we have identified markers that are specific for MSCs and their differentiated progeny. Further, we have also identified pathways that MSCs use to differentiate into adipogenic, chondrogenic, and osteogenic lineages. We identified activin-mediated transforming growth factor (TGF)-beta signaling, platelet-derived growth factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key pathways involved in MSC differentiation. The differentiation of MSCs into these lineages is affected when these pathways are perturbed by inhibitors of cell surface receptor function. Since growth and differentiation are tightly linked processes, we also examined the importance of these 3 pathways in MSC growth. These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of these pathways slowed MSC growth, whereas a combination of TGF-beta, PDGF, and beta-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages. Thus, this study illustrates it is possible to predict signaling pathways active in cellular differentiation and growth using microarray data and experimentally verify these predictions.