Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis.
Differentiating human multipotent mesenchymal stromal cells regulate microRNAs: prediction of microRNA regulation by PDGF during osteogenesis.
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DOI：
10.1016/j.exphem.2008.05.004
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发表时间：
2008-10
影响因子：
2.6
通讯作者：
Hart, Ronald P.
中科院分区：
文献类型：
--
作者：
Goff, Loyal A.;Boucher, Shayne;Ricupero, Christopher L.;Fenstermacher, Sara;Swerdel, Mavis;Chase, Lucas G.;Adams, Christopher C.;Chesnut, Jonathan;Lakshmipathy, Uma;Hart, Ronald P.
人多能间充质基质细胞（MSC）具有分化为多种细胞类型的潜力，尽管对控制其命运的因素知之甚少。分化特异性microRNA可能在干细胞自我更新和分化中发挥关键作用。我们提出，特定的细胞内信号通路通过调节microRNA表达来调节分化过程中的基因表达。对MSC及其分化后代进行Illumina mRNA和NCode microRNA表达分析。生物信息学预测和途径抑制的组合用于鉴定与PDGF信号传导相关的microRNA。MSC中的microRNA表达模式与多能干细胞如人胚胎干细胞中的microRNA表达模式不同。在MSC中，特定的microRNA群体在分化过程中被调节，靶向特定的细胞类型。互补mRNA表达分析增加了MSC或分化后代的标志物特征库。为了确定受信号通路影响的microRNA表达模式，我们通过微阵列研究检测了骨生成过程中受调控的PDGF通路。通过直接PDGF抑制实验证实了一组生物信息学预测响应PDGF信号传导的microRNA。我们的研究结果表明，在骨髓间充质干细胞成骨分化过程中调节的microRNA的子集是响应于PDGF通路的扰动。这种方法不仅识别了分化特异性mRNA和microRNA的特征类别，而且开始将受调控的分子与特定的细胞途径联系起来。
Human multipotent mesenchymal stromal cells (MSC) have the potential to differentiate into multiple cell types, although little is known about factors that control their fate. Differentiation-specific microRNAs may play a key role in stem cell self renewal and differentiation. We propose that specific intracellular signalling pathways modulate gene expression during differentiation by regulating microRNA expression. Illumina mRNA and NCode microRNA expression analyses were performed on MSC and their differentiated progeny. A combination of bioinformatic prediction and pathway inhibition was used to identify microRNAs associated with PDGF signalling. The pattern of microRNA expression in MSC is distinct from that in pluripotent stem cells such as human embryonic stem cells. Specific populations of microRNAs are regulated in MSC during differentiation targeted towards specific cell types. Complementary mRNA expression analysis increases the pool of markers characteristic of MSC or differentiated progeny. To identify microRNA expression patterns affected by signalling pathways, we examined the PDGF pathway found to be regulated during osteogenesis by microarray studies. A set of microRNAs bioinformatically predicted to respond to PDGF signalling was experimentally confirmed by direct PDGF inhibition. Our results demonstrate that a subset of microRNAs regulated during osteogenic differentiation of MSCs is responsive to perturbation of the PDGF pathway. This approach not only identifies characteristic classes of differentiation-specific mRNAs and microRNAs, but begins to link regulated molecules with specific cellular pathways.
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影响因子：
64.8
作者：
Hatfield, SD;Shcherbata, HR;Ruohola-Baker, H
通讯作者：
Ruohola-Baker, H
影响因子：
20.3
作者：
GRONTHOS, S;GRAVES, SE;SIMMONS, PJ
通讯作者：
SIMMONS, PJ
影响因子：
4
作者：
Gronthos, S;Zannettino, ACW;Simmons, PJ
通讯作者：
Simmons, PJ
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
--
作者：
Awad, HA;Butler, DL;Caplan, AI
通讯作者：
Caplan, AI