Human reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral infections.
Xinyu XiangYu TaoJonathan DiRussoFei-Man HsuJinchun ZhangZiwei XueJulien PontisDidier TronoWanlu LiuAmander T ClarkPublished in: Nature communications (2022)
Germ cells are essential to pass DNA from one generation to the next. In human reproduction, germ cell development begins with the specification of primordial germ cells (PGCs) and a failure to specify PGCs leads to human infertility. Recent studies have revealed that the transcription factor network required for PGC specification has diverged in mammals, and this has a significant impact on our understanding of human reproduction. Here, we reveal that the Hominidae-specific Transposable Elements (TEs) LTR5Hs, may serve as TEENhancers (TE Embedded eNhancers) to facilitate PGC specification. LTR5Hs TEENhancers become transcriptionally active during PGC specification both in vivo and in vitro with epigenetic reprogramming leading to increased chromatin accessibility, localized DNA demethylation, enrichment of H3K27ac, and occupation of key hPGC transcription factors. Inactivation of LTR5Hs TEENhancers with KRAB mediated CRISPRi has a significant impact on germ cell specification. In summary, our data reveals the essential role of Hominidae-specific LTR5Hs TEENhancers in human germ cell development.
Keyphrases
- germ cell
- endothelial cells
- transcription factor
- induced pluripotent stem cells
- skeletal muscle
- induced apoptosis
- pluripotent stem cells
- gene expression
- dna methylation
- dna damage
- cell fate
- cell cycle arrest
- cell death
- single cell
- single molecule
- adipose tissue
- deep learning
- cell free
- artificial intelligence
- big data
- case control