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人类内源性逆转录病毒-H 和 K 在人骨髓间充质干细胞中的表达作为干细胞特性的潜在标志物。

Human Endogenous Retrovirus-H and K Expression in Human Mesenchymal Stem Cells as Potential Markers of Stemness.

机构信息

Department of Public Health and Pediatric Sciences, Medical School, University of Turin, Turin, Italy.

Pediatric Onco-Hematology, Stem Cell Transplantation and Cell Therapy Division, City of Science and Health of Turin, Regina Margherita Children Hospital, Turin, Italy.

出版信息

Intervirology. 2019;62(1):9-14. doi: 10.1159/000499185. Epub 2019 May 17.

Abstract

OBJECTIVE

The human endogenous retroviruses (HERVs) are endogenous retroviruses that were inserted into the germ cell DNA of humans over 30 million years ago. Insertion of HERVs into the chromosomal DNA can influence a number of host genes in various modes during human evolution and their proviral long terminal repeats can participate in the transcriptional regulation of various cellular genes. Our aim was to evaluate the pol gene expression of HERV-K and HERV-H in mesenchymal stem cells (MSCs) in relation with the expression of stemness genes such as NANOG, OCT-4, and SOX-2.

METHODS

MSCs were isolated from bone marrow of healthy donors and expanded until the 5th passage in α-MEM with 10% fetal bovine serum. HERV-K, HERV-H pol gene, NANOG, OCT-4, SOX-2, and GAPDH expression was quantified by real-time PCR in MSCs during the expansion.

RESULTS

HERV-K and HERV-H expression was always higher at p1 compared to other passages and this difference reached a high statistical significance when passage p1 was compared with passage 3. In addition, NANOG, OCT-4, and SOX-2 expression at p1 was significantly higher than their expression at p3. Pearson's test demonstrated a strong correlation between the expression of HERV-K and HERV-H and the expression of NANOG, OCT-4, and SOX-2.

CONCLUSIONS

Our findings showed that HERV-K and H were concurrently expressed with pluripotency biomarkers NANOG, OCT-4, and SOX-2.

摘要

目的

人类内源性逆转录病毒(HERV)是在 3000 多万年前插入人类生殖细胞 DNA 的内源性逆转录病毒。HERV 插入染色体 DNA 可以在人类进化过程中以多种模式影响许多宿主基因,并且其前病毒长末端重复序列可以参与多种细胞基因的转录调控。我们的目的是评估间质干细胞(MSCs)中 HERV-K 和 HERV-H 的 pol 基因表达与干性基因(如 NANOG、OCT-4 和 SOX-2)的表达之间的关系。

方法

从健康供体的骨髓中分离 MSC,并在含 10%胎牛血清的 α-MEM 中扩增至第 5 代。通过实时 PCR 定量 MSC 扩增过程中 HERV-K、HERV-H pol 基因、NANOG、OCT-4、SOX-2 和 GAPDH 的表达。

结果

与其他传代数相比,HERV-K 和 HERV-H 在 p1 时的表达总是更高,当将 p1 与 p3 进行比较时,这种差异达到了高度统计学意义。此外,p1 时 NANOG、OCT-4 和 SOX-2 的表达明显高于 p3 时的表达。Pearson 检验表明 HERV-K 和 HERV-H 的表达与 NANOG、OCT-4 和 SOX-2 的表达之间存在很强的相关性。

结论

我们的研究结果表明,HERV-K 和 H 与多能性标志物 NANOG、OCT-4 和 SOX-2 同时表达。

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