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当将猕猴成纤维细胞转化为神经上皮干细胞时,转座元件的转录动力学。

Transcriptional dynamics of transposable elements when converting fibroblast cells of Macaca mulatta to neuroepithelial stem cells.

机构信息

Foshan Stomatology Hospital and School of Medicine, Foshan University, Foshan, Guangdong, 528000, China.

State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.

出版信息

BMC Genomics. 2021 Jun 4;22(Suppl 3):405. doi: 10.1186/s12864-021-07717-9.

Abstract

BACKGROUND

Transposable elements (TE) account for more than 50% of human genome. It has been reported that some types of TEs are dynamically regulated in the reprogramming of human cell lines. However, it is largely unknown whether some TEs in Macaca mulatta are also regulated during the reprogramming of cell lines of monkey.

RESULTS

Here, we systematically examined the transcriptional activities of TEs during the conversion of Macaca mulatta fibroblast cells to neuroepithelial stem cells (NESCs). Hundreds of TEs were dynamically regulated during the reprogramming of Macaca mulatta fibroblast cells. Furthermore, 48 Long Terminal Repeats (LTRs), as well as some integrase elements, of Macaca endogenous retrovirus 3 (MacERV3) were transiently activated during the early stages of the conversion process, some of which were further confirmed with PCR experiments. These LTRs were potentially bound by critical transcription factors for reprogramming, such as KLF4 and ETV5.

CONCLUSION

These results suggest that the transcription of TEs are delicately regulated during the reprogramming of Macaca mulatta fibroblast cells. Although the family of ERVs activated during the reprogramming of fibroblast cells in Macaca mulatta is different from those in the reprogramming of human fibroblast cells, our results suggest that the activation of some ERVs is a conserved mechanism in primates for converting fibroblast cells to stem cells.

摘要

背景

转座元件 (TE) 占人类基因组的 50%以上。据报道,某些类型的 TE 在人类细胞系的重编程中是动态调节的。然而,猕猴细胞系重编程过程中某些 TE 是否也受到调节,在很大程度上尚不清楚。

结果

在这里,我们系统地研究了 TE 在猕猴成纤维细胞向神经上皮干细胞 (NESCs) 转化过程中的转录活性。在猕猴成纤维细胞的重编程过程中,有数百个 TE 被动态调节。此外,猕猴内源性逆转录病毒 3 (MacERV3) 的 48 个长末端重复序列 (LTR) 和一些整合酶元件在转化过程的早期被短暂激活,其中一些通过 PCR 实验进一步证实。这些 LTR 可能被重编程的关键转录因子(如 KLF4 和 ETV5)结合。

结论

这些结果表明,TE 的转录在猕猴成纤维细胞的重编程过程中受到精细调控。尽管在猕猴成纤维细胞重编程过程中激活的 ERV 家族与在人类成纤维细胞重编程过程中激活的 ERV 家族不同,但我们的结果表明,一些 ERV 的激活是灵长类动物将成纤维细胞转化为干细胞的一种保守机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb4/8176597/ad518d54e982/12864_2021_7717_Fig1_HTML.jpg

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