Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells.
Histone demethylase JMJD6 regulates cellular migration and proliferation in adipose-derived mesenchymal stem cells.
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组蛋白去甲基化酶 JMJD6 调节脂肪间充质干细胞的细胞迁移和增殖
DOI：
10.1186/s13287-018-0949-3
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发表时间：
2018-08-09
影响因子：
7.5
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Shen C;Quan Q;Yang C;Wen Y;Li H
脂肪间充质干细胞(ADSCs)因其具有分化、增殖和迁移能力而被广泛开发为一种有前途的治疗剂。调控间充质干细胞(MSCs)命运的表观遗传学机制已被详细描述。然而，对ADSCs增殖和迁移的表观遗传调控知之甚少。本研究通过RT-PCR、siRNA筛选和芯片定量聚合酶链式反应检测了组蛋白去甲基酶的作用和表达。对shRNA介导的JMJD6基因敲除ADSCs和对照ADSCs进行细胞增殖和迁移实验。PDE1C抑制研究证实其在JMJD6介导的ADSCs表观遗传调控中的作用。这些数据表明，组蛋白去甲基酶JMJD6通过去除PDEC1启动子区域的H4R3me2a，抑制PDEC1的表达，在调控ADSCs的增殖和迁移中发挥关键作用。重要的是，在ADSCs中JMJD6的缺失显著增加了细胞的增殖和运动能力，这与PDE1C表达增加以及cAMP和cGMP水平降低有关。PDE1C抑制剂可以逆转增殖和迁移的增加，这表明JMJD6作为表观遗传调节因子减弱了ADSCs的增殖和迁移，PDE1C部分参与了JMJD6介导的调控。综上所述，我们的结果首次表明JMJD6通过调节PDE1C的表达在调控ADSCs的增殖和迁移中发挥重要作用。本文的在线版本(10.1186/s13287-0180949-3)包含向授权用户提供的补充材料。
Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic mechanisms that regulate the fate of mesenchymal stem cells (MSCs) have been described in detail. However, the epigenetic modulation of ADSCs proliferation and migration is poorly understood. The present study examined histone demethylases roles and expression by RT-PCR, as well as through siRNA screening and ChIP-qPCR assay. Cellular proliferation and migration assays were employed in shRNA-mediated JMJD6 knockdown and control ADSCs. PDE1C inhibition studies were conducted to confirm its role in JMJD6-mediated epigenetic regulation of ADSCs. The data demonstrate that the histone demethylase JMJD6 plays a critical role in regulating the proliferation and migration of ADSCs by removing H4R3me2a at the promoter regions of PDEC1 and suppressing PDEC1 expression. Importantly, the depletion of JMJD6 in ADSCs significantly increased cellular proliferation and motility, which was associated with increases in PDE1C expression and decreases in the levels of both cAMP and cGMP. The increase in proliferation and migration was reversed by treatment with a PDE1C inhibitor, suggesting that JMJD6 attenuates the proliferation and migration of ADSCs as an epigenetic regulator and PDE1C partially contributes to the JMJD6-mediated regulation. Taken together, our results indicate for the first time that JMJD6 plays an important role in the regulation of ADSCs proliferation and migration through the modulation of PDE1C expression. The online version of this article (10.1186/s13287-018-0949-3) contains supplementary material, which is available to authorized users.
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影响因子：
4.8
作者：
Han, P;Werber, J;Michaeli, T
通讯作者：
Michaeli, T
影响因子：
3.7
作者：
Li A;Xia X;Yeh J;Kua H;Liu H;Mishina Y;Hao A;Li B
通讯作者：
Li B
影响因子：
64.8
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
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影响因子：
5.2
作者：
Du, Juan;Ma, Yushi;Fan, Zhipeng
通讯作者：
Fan, Zhipeng
DOI：
10.1007/978-94-007-2016-9_34
发表时间：
2012-01-01
期刊：
STEM CELLS AND CANCER STEM CELLS: THERAPEUTIC APPLICATIONS IN DISEASE AND INJURY
影响因子：
--
作者：
Kakudo, Natsuko;Kushida, Satoshi;Kusumoto, Kenji
通讯作者：
Kusumoto, Kenji