Technology to the rescue: how to uncover the role of transposable elements in preimplantation development

Abstract

Transposable elements (TEs) are highly expressed in preimplantation development. Preimplantation development is the phase when the cells of the early embryo undergo the first cell fate choice and change from being totipotent to pluripotent. A range of studies have advanced our understanding of TEs in preimplantation, as well as their epigenetic regulation and functional roles. However, many questions remain about the implications of TE expression during early development. Challenges originate first due to the abundance of TEs in the genome, and second because of the limited cell numbers in preimplantation. Here we review the most recent technological advancements promising to shed light onto the role of TEs in preimplantation development. We explore novel avenues to identify genomic TE insertions and improve our understanding of the regulatory mechanisms and roles of TEs and their RNA and protein products during early development.

Keywords: epigenetics; gene regulation; preimplantation development; transposable elements.

Figure 1.

Schematic of TEs expressed at stages of preimplantation development. Adapted from [5,6]. Created with BioRender.com

Figure 2.. Technology for Transposable elements — Schematic of key technologies for the study various aspects of TE and preimplantation biology.

CasID: Cas9-targeted biotinylation of TE-bound proteins, followed by streptavidin pulldown and Liquid Chromatography-Mass Spectrometry (LC-MS) for protein identification [11]. CELLOseq: addition of cellular barcodes and unique molecular identifiers (UMIs) enables single-cell long-read RNA sequencing for unique mapping of TE-derived transcripts [8]. Spatial Transcriptomics: hybridisation of unique oligos across the sample prior to imaging and RNA isolation enables coupling of imaging with transcriptomic analysis [12]. DiMeLo-seq: Antibody-targeted DNA methyltransferases result in enrichment of m6dA over protein-bound regions which can be resolved with ONT direct DNA sequencing [13]. STARR-seq: genome fragmentation and generation of many reporter constructs is followed by RNA extraction and enrichment analysis for enhancer identification [14]. Created with BioRender.com.