MicroRNA-34a modulates genes involved in cellular motility and oxidative phosphorylation in neural precursors derived from human umbilical cord mesenchymal stem cells.
MicroRNA-34a modulates genes involved in cellular motility and oxidative phosphorylation in neural precursors derived from human umbilical cord mesenchymal stem cells.
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DOI：
10.1186/1755-8794-4-65
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发表时间：
2011-09-19
影响因子：
2.7
通讯作者：
Wang HW
中科院分区：
文献类型：
--
作者：
Chang SJ;Weng SL;Hsieh JY;Wang TY;Chang MD;Wang HW
骨髓 (BM-MSC) 和人脐带沃顿氏胶基质 (WJ-MSC) 中发现的间充质干细胞 (MSC) 能够在体外和体内转分化为神经元谱系细胞，因此具有治疗中风或帕金森病等神经疾病的潜力。在骨髓 MSC 中，miR-130a 和 miR-206 已被证明可以调节人间充质干细胞衍生的神经元细胞中神经递质 P 物质的合成。然而，WJ-MSC 中神经元分化是如何控制的仍不清楚。 WJ-MSCs 是从人脐带中分离出来的。我们通过已发布的方案将 WJ-MSC 置于神经发生中，并通过安捷伦 microRNA 微阵列分析 WJ-MSC 及其神经元祖细胞（分化后第 9 天）的 miRNAome 模式。 WJ-MSC 中富集了 5 种 miRNA，包括 miR-345、miR-106a、miR-17-5p、miR-20a 和 miR-20b。另外 11 种 miRNA（miR-206、miR-34a、miR-374、miR-424、miR-100、miR-101、miR-323、miR-368、miR-137、miR-138 和 miR-377）在转分化的神经祖细胞中大量表达。在这些 miRNA 中，miR-34a 和 miR-206 是仅有的 2 个与 BM-MSC 神经发生相关的 miRNA。细胞中过度表达 miR-34a 会抑制 136 个神经元祖基因的表达，这些基因都具有假定的 miR-34a 结合位点。根据Gene Ontology数据库进行的基因富集分析显示，这136个基因与细胞运动、能量产生（包括氧化磷酸化、电子传递和ATP合成）和肌动蛋白细胞骨架组织相关，表明miR-34a在前体细胞迁移中发挥着关键作用。敲低 WJ-MSC 中的内源性 miR-34a 表达会导致 WJ-MSC 运动性增强。我们的数据表明 miRNA 在 MSC 神经元分化中发挥着关键作用，而 miR-34a 有助于神经元前体运动，这对于干细胞归巢到其应有的靶位点可能至关重要。
Mesenchymal stem cell (MSC) found in bone marrow (BM-MSCs) and the Wharton's jelly matrix of human umbilical cord (WJ-MSCs) are able to transdifferentiate into neuronal lineage cells both in vitro and in vivo and therefore hold the potential to treat neural disorders such as stroke or Parkinson's disease. In bone marrow MSCs, miR-130a and miR-206 have been show to regulate the synthesis of neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. However, how neuronal differentiation is controlled in WJ-MSC remains unclear. WJ-MSCs were isolated from human umbilical cords. We subjected WJ-MSCs into neurogenesis by a published protocol, and the miRNome patterns of WJ-MSCs and their neuronal progenitors (day 9 after differentiation) were analyzed by the Agilent microRNA microarray. Five miRNAs were enriched in WJ-MSCs, including miR-345, miR-106a, miR-17-5p, miR-20a and miR-20b. Another 11 miRNAs (miR-206, miR-34a, miR-374, miR-424, miR-100, miR-101, miR-323, miR-368, miR-137, miR-138 and miR-377) were abundantly expressed in transdifferentiated neuronal progenitors. Among these miRNAs, miR-34a and miR-206 were the only 2 miRNAs been linked to BM-MSC neurogenesis. Overexpressing miR-34a in cells suppressed the expression of 136 neuronal progenitor genes, which all possess putative miR-34a binding sites. Gene enrichment analysis according to the Gene Ontology database showed that those 136 genes were associated with cell motility, energy production (including those with oxidative phosphorylation, electron transport and ATP synthesis) and actin cytoskeleton organization, indicating that miR-34a plays a critical role in precursor cell migration. Knocking down endogenous miR-34a expression in WJ-MSCs resulted in the augment of WJ-MSC motility. Our data suggest a critical role of miRNAs in MSC neuronal differentiation, and miR-34a contributes in neuronal precursor motility, which may be crucial for stem cells to home to the target sites they should be.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
DOI：
10.4161/cc.9.6.10987
发表时间：
2010-03-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Guessous F;Zhang Y;Kofman A;Catania A;Li Y;Schiff D;Purow B;Abounader R
通讯作者：
Abounader R
影响因子：
14.9
作者：
Harris, MA;Clark, J;White, R
通讯作者：
White, R
影响因子：
4
作者：
Hsieh, Jui-Yu;Fu, Yu-Show;Wang, Hsei-Wei
通讯作者：
Wang, Hsei-Wei
影响因子：
4
作者：
Bertani, N;Malatesta, P;Perris, R
通讯作者：
Perris, R