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ERV6 的长末端重复序列在食蟹猴的植入前胚胎中被激活。

The Long Terminal Repeats of ERV6 Are Activated in Pre-Implantation Embryos of Cynomolgus Monkey.

机构信息

Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China.

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.

出版信息

Cells. 2021 Oct 9;10(10):2710. doi: 10.3390/cells10102710.

DOI:10.3390/cells10102710
PMID:34685690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8534818/
Abstract

Precise gene regulation is critical during embryo development. Long terminal repeat elements (LTRs) of endogenous retroviruses (ERVs) are dynamically expressed in blastocysts of mammalian embryos. However, the expression pattern of LTRs in monkey blastocyst is still unknown. By single-cell RNA-sequencing (seq) data of cynomolgus monkeys, we found that LTRs of several ERV families, including MacERV6, MacERV3, MacERV2, MacERVK1, and MacERVK2, were highly expressed in pre-implantation embryo cells including epiblast (EPI), trophectoderm (TrB), and primitive endoderm (PrE), but were depleted in post-implantation. We knocked down MacERV6-LTR1a in cynomolgus monkeys with a short hairpin RNA (shRNA) strategy to examine the potential function of MacERV6-LTR1a in the early development of monkey embryos. The silence of MacERV6-LTR1a mainly postpones the differentiation of TrB, EPI, and PrE cells in embryos at day 7 compared to control. Moreover, we confirmed MacERV6-LTR1a could recruit Estrogen Related Receptor Beta (ESRRB), which plays an important role in the maintenance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF and Wnt signaling pathways. In summary, these results suggest that MacERV6-LTR1a is involved in gene regulation of the pre-implantation embryo of the cynomolgus monkeys.

摘要

精确的基因调控在胚胎发育过程中至关重要。内源性逆转录病毒 (ERV) 的长末端重复元件 (LTR) 在哺乳动物胚胎的囊胚中动态表达。然而，猴囊胚中 LTR 的表达模式尚不清楚。通过对食蟹猴的单细胞 RNA 测序 (seq) 数据进行分析，我们发现包括 MacERV6、MacERV3、MacERV2、MacERVK1 和 MacERVK2 在内的几个 ERV 家族的 LTR 在包括上胚层 (EPI)、滋养外胚层 (TrB) 和原始内胚层 (PrE) 在内的着床前胚胎细胞中高度表达，但在着床后被耗尽。我们使用短发夹 RNA (shRNA) 策略敲低食蟹猴中的 MacERV6-LTR1a，以研究 MacERV6-LTR1a 在猴胚胎早期发育中的潜在功能。与对照相比，MacERV6-LTR1a 的沉默主要推迟了第 7 天胚胎中 TrB、EPI 和 PrE 细胞的分化。此外，我们证实 MacERV6-LTR1a 可以募集雌激素相关受体β (ESRRB)，它通过包括 FGF 和 Wnt 信号通路在内的不同信号通路在胚胎和滋养层干细胞的自我更新和多能性维持中发挥重要作用。总之，这些结果表明 MacERV6-LTR1a 参与了食蟹猴着床前胚胎的基因调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/cbc80628de6a/cells-10-02710-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/15fbd4aa21b6/cells-10-02710-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/bae8050017da/cells-10-02710-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/1ecbb39299c1/cells-10-02710-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/603b7d2c4d2c/cells-10-02710-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/e330f557b0a7/cells-10-02710-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/cbc80628de6a/cells-10-02710-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/15fbd4aa21b6/cells-10-02710-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/bae8050017da/cells-10-02710-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/1ecbb39299c1/cells-10-02710-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/603b7d2c4d2c/cells-10-02710-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/e330f557b0a7/cells-10-02710-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/257b/8534818/cbc80628de6a/cells-10-02710-g006.jpg

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