Circular RNAs are abundantly expressed and upregulated during repair of the damaged endometrium by Wharton's jelly-derived mesenchymal stem cells.

Circular RNAs are abundantly expressed and upregulated during repair of the damaged endometrium by Wharton's jelly-derived mesenchymal stem cells.
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沃顿胶来源的间充质干细胞修复受损子宫内膜期间,环状 RNA 大量表达并上调

DOI:
10.1186/s13287-018-1046-3
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发表时间:
2018-11-15
影响因子:
7.5
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学2区
文献类型:
--
作者:
Sun B;Shi L;Shi Q;Jiang Y;Su Z;Yang X;Zhang Y

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沃顿商学院的骨髓间充质干细胞(WJ-MSCs)在修复不同疾病方面表现出强大的潜力。环状RNA(circRNA)的表达谱为修复过程的调控和修复作用机制的探索提供了有价值的见解。将米非司酮与人子宫内膜基质细胞(ESCs)共同培养,获得受损ESCs,并与WJ-MSCs共培养或不共培养(共培养组与非共培养组),观察WJ-MSCs对受损ESCs的修复作用。采用CircRNA芯片对两组进行比较。基于转录组学数据,采用基因本体论(GO)、京都基因与基因组百科全书(KEGG)途径和网络分析方法对两组的差异基因表达谱进行分析。对circRNA数据库进行筛选,并通过定量聚合酶链反应(qPCR)确认结果。WJ-MSCs对损伤的ESCs具有修复作用,表现为细胞形态改善,增殖能力增强,凋亡率降低。CircRNA芯片显示,共培养组中有7757条circRNA在ESCs中有差异表达。两组中GO上调的细胞周期、细胞周期进程和核分裂均居首位,而DNA复制和细胞周期在两组中KEGG通路分析上调的细胞周期均居首位。通过微阵列分析,在同一组样品中选择9种最异常表达的circRNA用于进一步验证。在共培养组中,9种最异常的circRNA中有7种被证实显著上调。通过qPCR,7种circRNA中的4种(hsa_circ_0015825、hsa-circRNA 4049 -38、hsa-circRNA 5028 -15和hsa_circ_0111659)在ESC和WJ-MSC中的表达均随着时间的推移而趋于降低。其余三种circRNA(hsa-circRNA 8881 -21、hsa_circ_0020492和hsa_circ_0026141)的水平在ESC或WJ-MSC中均未随时间发生显著变化。此外,我们重点关注hsa_circRNA_0111659,并预测其miRNA和靶向mRNA。circRNA-miRNA-mRNA的联合可能参与调节子宫内膜损伤的修复。我们的研究结果显示了WJ-MSCs修复受损子宫内膜过程中丰富且上调的circRNA谱,为circRNA在WJ-MSCs修复子宫内膜过程中的调控提供了新的视角。本文的在线版本(10.1186/s13287-018-1046-3)包含补充材料,可供授权用户使用。
Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exhibit strong and powerful potential in repairing different diseases. The expression profile of circular RNA (circRNA) provides valuable insight for regulation of the repair process and exploration of reparative effect mechanisms. Human endometrial stromal cells (ESCs) were cultured with mifepristone to obtain damaged ESCs, which were then cocultured with or without WJ-MSCs (cocultured group versus non-cocultured group) to observe the reparative effect upon damaged ESCs by WJ-MSCs. CircRNA microarray was performed between the two groups. Based on the transcriptomics data, the differential gene expression profiles of the two groups were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and network analysis methods. Screening of a circRNA database was performed, and the results were confirmed by quantitative polymerase chain reaction (qPCR). WJ-MSCs exerted a reparative effect upon damaged ESCs in the cocultured group such as improved cell morphology, higher proliferative ability, and lower apoptosis rate. CircRNA array showed that 7757 circRNAs were differentially expressed in ESCs from the cocultured group. Mitotic cell cycle, cell cycle process, and nuclear division ranked top in the GO upregulated list of the two groups, while DNA replication and cell cycle ranked top in the KEGG pathway analysis upregulated list of the two groups. The nine most aberrantly expressed circRNAs were selected for further verification in the same cohort of samples by microarray analysis. Seven of the nine most aberrantly circRNAs were confirmed to be significantly upregulated in the cocultured group. And four of the seven circRNAs (hsa_circ_0015825, hsa-circRNA4049-38, hsa-circRNA5028-15, and hsa_circ_0111659) expression both in ESCs and WJ-MSCs tended to decrease with time by qPCR. The levels of the remaining three circRNAs (hsa-circRNA8881-21, hsa_circ_0020492 and hsa_circ_ 0026141) did not change significantly over time in either ESCs or WJ-MSCs. Moreover, we focused on hsa_circRNA_0111659 and predicted its miRNAs and targeted mRNA. The association of circRNA-miRNA-mRNA is likely to be involved in regulating the repair of endometrial damage. Our results presented the abundant and upregulated circRNAs profile during repair of the damaged endometrium by WJ-MSCs and provided a novel perspective for circRNAs in the regulation of WJ-MSCs for endometrial repair. The online version of this article (10.1186/s13287-018-1046-3) contains supplementary material, which is available to authorized users.
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