Human endogenous retroviruses aid embryonic development [article]

Manvendra Singh, Universitätsbibliothek Der FU Berlin, Universitätsbibliothek Der FU Berlin
Human genome has been expanded to approximately 8% by multiple waves of retroviral invasions, followed by lateral expansion, mainly in germ cells. Recent advancements provide substantial evidence that few families of Human Endogenous Retro-Viruses (HERVs) are co-opted to regulate cell-type specific physiological networks. Following up, we show that diverse modes of HERV-H activity have played a pivotal role in the evolution and development of human- specific embryogenesis including
more » ... HERV-H provides binding sites for pluripotency transcription factors and serves as a major source for ncRNAs and chimeric transcripts in hPSCs. The interplay of host kruepel box proteins with HERV- H transcription determines the stability of human pluripotency. We updated the transcriptomic and transposcriptomic atlas of Human Preimplantation Embryogenesis (HPE) that re-define the progression of HPE at single-cell resolution. We characterize an unattended cell population in HPE that did not commit to any of the known lineages to form a stable preimplantation blastocyst. ICM being considered as reference frame for the purity of hESCs in naive/primed state conflict, we redefine ICM which adds another layer to the understanding of basic and regenerative biology. Committed and non-committed cells are distinguished by the reactivation of full-length HERVs and mutagenic retrotransposons respectively. We show that HERV-H transcripts control younger mutagenic elements with the mechanisms not known to us yet. Additionally, we also show that HERV-H expression is also prominent during fertilization and early stage of embryogenesis. We find the contrasting pattern of distinct loci of HERV-H during HPE, few of them driving the stage-specific markers that might determine the commitment of host cells to pluripotent lineages. Upon comparing the embryonic lineages and pluripotent states between primates, we decipher the probable mechanisms shaping the human-specific nature of embryogenesis. Much divergence within primate early development [...]
doi:10.17169/refubium-1312 fatcat:lwvuvlafava3vdgj6u5nxkxtw4