A hominoid-specific endogenous retrovirus has rewired the gene regulatory network shared between primordial germ cells and naïve pluripotent cells

Although the gene regulatory networks of germ cells are critical for gamete integrity, these networks have been diversified during mammalian evolution. Here, we show that numerous copies of LTR5_Hs, a hominoid-specific endogenous retrovirus (ERV), function as enhancers in both human primordial germ cells (PGCs) and naïve pluripotent cells. Multiomics analysis suggested that PGCs and naïve pluripotent cells exhibit a similar transcriptome signature, and enhancers derived from LTR5_Hs contribute to establishing such similarity. LTR5_Hs appears to be activated by transcription factors critical in both cell types (KLF4, TFAP2C, NANOG, and CBFA2T2). Comparative transcriptome analysis between humans and macaques suggested that the expression of many genes in PGCs and naïve pluripotent cells has been upregulated by LTR5_Hs insertions in the hominoid lineage. Together, this study suggests that LTR5_Hs insertions have rewired and finetuned the gene regulatory network shared between PGCs and naïve pluripotent cells during hominoid evolution.