Differential regulation of transposable elements (TEs) during the murine submandibular gland development

Abstract

The submandibular gland (SG) is a relatively simple organ formed by three cell types: acinar, myoepithelial, and an intricate network of duct-forming epithelial cells, that together fulfills several physiological functions from assisting food digestion to acting as an immune barrier against pathogens. Successful SG organogenesis is the product of highly controlled and orchestrated genetic and transcriptional programs. Mounting evidence links Transposable Elements (TEs), originally thought to be selfish genetic elements, to different aspects of gene regulation in mammalian development and disease. To our knowledge, the role of TEs during murine SG organogenesis has not been studied. Using novel bioinformatic tools and publicly available RNA-Seq datasets, our results indicate that a significant number of genic and intergenic TEs are differentially expressed during the SG development. Furthermore, changes in expression of specific TEs correlated with that of genes involved in cellular division and differentiation, critical aspects for SG maturation. Altogether, we propose that TEs modulate gene networks that operate during SG development.

Transposable Elements are differentially activated in cell lineages during the developing murine submandibular gland

“…This was also a concern in our previous bulk RNA-Seq study, where the RNA selection protocol was based on polyA selection. In turn, we demonstrated that under these conditions, approximately ~70% of all TEs could be retrieved (15). Interestingly, another reports have revealed a similar finding, in that such polyA-selection protocol might hinder detection of other repetitive elements, such as satellites, but not of TEs (35,36).…”

“…We have previously analyzed TE expression in the murine SMG using bulk RNA-Seq. Briefly, we found that more than 9000 TEs became differentially regulated across the E14.5, E16.5, E18.5, P1, P28 and P70 timepoints (15). Moreover, through statistical association analysis, we predicted genes that could be potentially modulated by TEs.…”

“…Although in all cases except P1, the proportion of these TEs is relatively low, I still highlight this result, due to its relevance to identify neighboring genes to those TEs, whose expression might be modulated by them. In turn, each of the locus-specific TE markers was associated to their closest gene, in order to predict their regulatory impact at the pathway level (Figure 8), following a similar approach to that of previous works (12,15,25,26). Most TE-related genes did not have an associated pathway, making it difficult to identify their potential consequences (Supplementary Table 2).…”

“…TEs have the ability to transpose either via a "copy-andpaste" mechanism (i.e., through reverse transcription of their mRNAs), as in the case of the Long Terminal Repeats (LTRs), Long Interspersed Nuclear Elements (LINEs) and Short Interspersed Nuclear Elements (SINEs); or via a "cut-and-paste" mechanisms (i.e., excision of the TE from its original genomic location and insertion elsewhere) as in the case of the DNA TEs (14). In mouse, the distribution of TEs is 41.9% SINE, 27.0% LINE, 26.6% LTR and 4.5% DNA (15). Across evolutionary timescales, most TEs have accumulated mutations that impede their functional activity (10).…”

The spatial and cellular portrait of Transposable Element expression during Gastric Cancer

“…Although most TEs are now genetically fixed, they can still become transcriptionally active, which can impact gene regulation 25 . Current evidence supports their role as regulatory elements in health and disease [26][27][28] . In particular, there are many examples of their global derepression and subsequent activation in a wide array of cancer types (reviewed in 29 ).…”