Transposable Elements in Pluripotent Stem Cells and Human Disease

Abstract

Transposable elements (TEs) are mobile genetic elements that can randomly integrate into other genomic sites. They have successfully replicated and now occupy around 40% of the total DNA sequence in humans. TEs in the genome have a complex relationship with the host cell, being both potentially deleterious and advantageous at the same time. Only a tiny minority of TEs are still capable of transposition, yet their fossilized sequence fragments are thought to be involved in various molecular processes, such as gene transcriptional activity, RNA stability and subcellular localization, and chromosomal architecture. TEs have also been implicated in biological processes, although it is often hard to reveal cause from correlation due to formidable technical issues in analyzing TEs. In this review, we compare and contrast two views of TE activity: one in the pluripotent state, where TEs are broadly beneficial, or at least mechanistically useful, and a second state in human disease, where TEs are uniformly considered harmful.

Cryptic endogenous retrovirus subfamilies in the primate lineage

“…This can impact the regulatory activity of nearby gene expression, and contribute to the adaptation of the LTRs in the host genome (Grow et al 2015; Chuong, Elde, and Feschotte 2017; Fueyo et al 2022). Additionally, ERVs have a higher chance of survival in the next generation when they are expressed in germline or pluripotent cells during early embryonic development (Gerdes et al 2016; Ma et al 2022; Göke et al 2015). In fact, several LTRs contain binding sequences for pluripotency transcription factors such as POU5F1 and SOX2 (Kunarso et al 2010; Fueyo et al 2022).…”