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MED31参与调节人间充质干细胞的自我更新和脂肪生成。

MED31 involved in regulating self-renewal and adipogenesis of human mesenchymal stem cells.

作者信息

Beadle Erik P, Straub Joseph A, Bunnell Bruce A, Newman Jamie J

机构信息

School of Biological Sciences, Louisiana Tech University, Ruston, LA, USA.

Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA, USA.

出版信息

Mol Biol Rep. 2018 Oct;45(5):1545-1550. doi: 10.1007/s11033-018-4241-5. Epub 2018 Jul 13.

DOI:10.1007/s11033-018-4241-5
PMID:30006772
Abstract

Regulation of gene expression is critical for the maintenance of cell state and homeostasis. Aberrant regulation of genes can lead to unwanted cell proliferation or misdirected differentiation. Here we investigate the role of MED31, a highly conserved subunit of the Mediator complex, to determine the role this subunit plays in the maintenance of human mesenchymal stem cell (hMSC) state. Using siRNA-mediated knockdown of MED31 we demonstrate a decrease in self-renewal based on cell assays and monitoring of gene expression. In addition, in the absence of MED31, hMSCs also displayed a reduction in adipogenesis as evidenced by diminished lipid vesicle formation and expression of specific adipogenic markers. These data present evidence for a significant role for MED31 in maintaining adult stem cell homeostasis, thereby introducing potential novel targets for future investigation and use in better understanding stem cell behavior and adipogenesis.

摘要

基因表达调控对于维持细胞状态和体内平衡至关重要。基因的异常调控会导致不必要的细胞增殖或分化方向错误。在此,我们研究中介体复合物的一个高度保守亚基MED31的作用,以确定该亚基在维持人间充质干细胞(hMSC)状态中所起的作用。通过小干扰RNA(siRNA)介导敲低MED31,我们基于细胞检测和基因表达监测证明了自我更新能力下降。此外,在缺乏MED31的情况下,hMSC的脂肪生成也减少,脂质小泡形成减少以及特定脂肪生成标志物的表达降低证明了这一点。这些数据表明MED31在维持成体干细胞体内平衡中具有重要作用,从而为未来的研究引入了潜在的新靶点,有助于更好地理解干细胞行为和脂肪生成。

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本文引用的文献

1
The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.核孔相关的TREX-2复合物利用中介体来调节基因表达。
Cell. 2015 Aug 27;162(5):1016-28. doi: 10.1016/j.cell.2015.07.059.
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MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31.微小RNA-1通过靶向中介因子1和中介因子31在骨肉瘤中发挥潜在的肿瘤抑制作用。
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Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.
转录中介体复合物的亚基结构与功能模块重排
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Gene expression profile of the whole Mediator complex in human osteosarcoma and normal osteoblasts.人骨肉瘤和正常成骨细胞中整个中介复合物的基因表达谱。
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SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function.需要 SIMPL 增强肿瘤坏死因子-α 依赖性 p65-MED1 复合物的形成,以维持哺乳动物造血干细胞和祖细胞的功能。
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6
Sox10 cooperates with the mediator subunit 12 during terminal differentiation of myelinating glia.Sox10 与中介体亚基 12 在髓鞘形成胶质细胞的终末分化过程中合作。
J Neurosci. 2013 Apr 10;33(15):6679-90. doi: 10.1523/JNEUROSCI.5178-12.2013.
7
Mutations in MED12 cause X-linked Ohdo syndrome.MED12 基因突变导致 X 连锁型 Ohdo 综合征。
Am J Hum Genet. 2013 Mar 7;92(3):401-6. doi: 10.1016/j.ajhg.2013.01.007. Epub 2013 Feb 7.
8
MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling.MED12 突变将智力障碍综合征与 GLI3 依赖性 Sonic Hedgehog 信号通路失调联系起来。
Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19763-8. doi: 10.1073/pnas.1121120109. Epub 2012 Oct 22.
9
Dual origin of mesenchymal stem cells contributing to organ growth and repair.间质干细胞的双重起源有助于器官生长和修复。
Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6503-8. doi: 10.1073/pnas.1015449108. Epub 2011 Apr 4.
10
Mediator and cohesin connect gene expression and chromatin architecture.中介体和黏合蛋白连接基因表达和染色质结构。
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