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Valdebenito-Maturana, B.

Publications and source records attributed to Valdebenito-Maturana, B..

3 recordsLinked to original sources

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

Gastric Cancer (GC) is a lethal malignancy, with urgent need for the discovery of novel biomarkers for its early detection. I previously showed that Transposable Elements (TEs) become activated in early GC (EGC), suggesting a role in gene expression. Here, I follow-up on that evidence using single-cell data from gastritis to EGC, and show that TEs are expressed and follow the disease progression, with 2,430 of them being cell populations markers. Pseudotemporal trajectory modeling revealed 111 TEs associated with the origination of cancer cells. Analysis of spatial data from GC also confirms TE expression, with 204 TEs being spatially enriched. Finally, a network of TE-mediated gene regulation was modeled, indicating that [~]2,000 genes could be modulated by TEs, with [~]500 of them already implicated in cancer. These results suggest that TEs might play a functional role in GC progression, and highlights them as potential biomarker for its early detection.

bioinformatics↗

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

The murine submandibular gland (SMG) is a model organ to study development, because it follows a branching morphogenesis pattern that is similar to that of lung, kidney, and other systems. It has been speculated that through its study, insights into regeneration and cancer could be obtained. Previously, using bulk RNA-Seq data, we reported that Transposable Elements (TEs) become activated during the SMG development. However, an outstanding question was as to whether their activity influenced different cell populations. Here, taking advantage of a single cell RNA-Seq atlas of the developing SMG, I studied TE expression to find out whether their activity can be recapitulated across its development, and if so, how they influenced cell types and cell fate specification. In this work, I found a total of 339 TEs that are markers of different cell populations, and then, through the modeling of the SMG development using Trajectory Inference methods, I found 2 TEs that could be potentially influencing differentiation processes. In sum, this short report reveals that TEs may be involved in the normal development of the SMG, and it highlights the importance of considering them in scRNA-Seq studies.

developmental biology↗

Activation Of Transposable Elements Upon Statin Treatment

High cholesterol levels have been associated with cardiovascular diseases, and lowering them has been a key focus in the treatment of such diseases. Statins are drugs used with that aim, and can be divided in the lipophilic Simvastatin and the hydrophilic Rosuvastatin. Regardless of the statin type, a high proportion ([~]70%) of patients stop using statins due to suffering from side effects on skeletal muscle, such as myalgia, and muscle cramps. Thus, there has been a considerable effort in understanding how statins contribute to these side effects. A catalogue of genes and molecular pathways that change upon statin treatment has been recently published, allowing further understanding how the side effects occur. However, Transposable Elements (TEs) were not studied. TEs can move within a genome, and they are highly repetitive, representing about half of the human genome. Currently, most TEs in the human genome are inactive, but it has been shown that TEs can still transcribe, and that either via their transposition or their transcriptional activity, can influence gene expression. Here, using novel computational tools to accurately estimate TE expression, we studied their activity and predicted their potential impact on gene expression. We developed a catalogue of TEs expressed upon statin treatment, and the putative genes whose expression might be influenced by TEs. Overall, we speculate that based on our findings, TEs might be a key target in order to understand statin-mediated side effects.

bioinformatics↗