Spatially Resolved Expression of Transposable Elements in Disease and Somatic Tissue with SpatialTE

Valdebenito-Maturana, Braulio; Guatimosim, Cristina; Carrasco, Mónica A.; Tapia, Juan Carlos

doi:10.3390/ijms222413623

Cited by 6 publications

(6 citation statements)

References 30 publications

(41 reference statements)

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“…In contrast, DNA transposons encode proteins that allow excision from the genome locus and its insertion elsewhere. Most TEs are unable to transpose as a result of the accumulation of inactivating mutations, and, based on their divergence rate, they can also be classified into "young" or "old" TEs [13,14]. In addition to inactivating mutations, host genomes have several mechanisms to regulate TE expression at the transcriptional and post-transcriptional level, such as DNA methylation, chromatin modifications, RNA interference pathways and through activity of Krüppel-associated box (KRAB) zinc-finger proteins, amongst others (reviewed in [15,16]).…”

Section: Introductionmentioning

confidence: 99%

Activation of Transposable Elements in Human Skeletal Muscle Fibers upon Statin Treatment

Valdebenito-Maturana

Carrasco

et al. 2022

IJMS

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High cholesterol levels have been linked to a high risk of cardiovascular diseases, and preventative pharmacological care to lower cholesterol levels is critically important. Statins, which are hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are drugs used to reduce the endogenous cholesterol synthesis, thus minimizing its pathophysiological effects. Despite the proven benefits, statins therapy is known to cause a number of skeletal muscle disorders, including myalgia, myopathy and myositis. The mechanisms underlying such statin-induced side effects are unknown. Recently, a group of genes and molecular pathways has been described to participate in statin-induced myopathy, caused by either simvastatin or rosuvastatin, although the mechanism by which changes in gene regulation occur was not studied. Transposable Elements (TEs), repetitive elements that move within the genome, are known to play regulatory roles in gene expression; however, their role in statin-induced muscle damage has not been studied. We analyzed the expression of TEs in human skeletal fiber cells treated with either simvastatin or rosuvastatin, as well as their respective controls, and identified TEs that change their expression in response to the treatment. We found that simvastatin resulted in >1000 differentially expressed (DE) TEs, whereas rosuvastatin resulted in only 27 DE TEs. Using network analysis tools, we predicted the impact of the DE TEs on the expression of genes and found that amongst the genes potentially modulated by TEs, there are some previously associated to statin-linked myopathy pathways (e.g., AKT3). Overall, our results indicate that TEs may be a key player in the statin-induced muscle side effects.

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Section: Introductionmentioning

confidence: 99%

Activation of Transposable Elements in Human Skeletal Muscle Fibers upon Statin Treatment

Valdebenito-Maturana

Carrasco

et al. 2022

IJMS

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“…Interestingly, LINEs and LTRs were expressed also at the P30 and Adult stages. Although TE expression was thought to only occur at early developmental stages as consequences of global epigenetic derepression, and in disease and stress conditions, as consequence of cellular malfunction, we and others have shown that they indeed become transcriptionally active in both mouse and human healthy, adult tissues (20,24). Such reports suggest that TEs could have functional implications in normal and proper cell functioning.…”

Section: Te Expression Across the Scrna-seq Atlas Of The Murine Smg D...mentioning

confidence: 69%

“…These reads are subsequently classified into one of the following categories based on the number of mapping locations: locus-specific, if the MAPQ is equal to 255 (indicating unique alignment), or subfamilyspecific, if the MAPQ was less than 255 (indicating multiple alignment). We have previously taken advantage of the usage of this metric in Spatial Transcriptomics data, which follows a similar computational process during alignment and demultiplexing, to that of scRNA-Seq (20). Although not all TE locus are retrieved, it still shows an improvement to the default strategy of directly summarizing expression at the subfamily level (12).…”

Section: Methodsmentioning

confidence: 99%

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

Valdebenito-Maturana¹

2023

Preprint

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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 regeneraration 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.

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“…83 Valdebenito-Maturana et al carried out a spatial expression analysis of transposable elements (TEs), developed SpatialTE tools, and applied them to the spinal cord data of ALS-infected mice. 95 Interestingly, the expression of TEs in the dorsal and ventral horns was higher than that observed in the medial or distal regions of the spinal cord. Some LTR and non-LTR TE (such as LINE and SINE) were activated in the disease.…”

Section: Application Of Spatial Transcriptomics (St) In Scimentioning

confidence: 90%

“…Further validation of clinical samples found that sphingomyelin signal can be used as a therapeutic target for ALS 83 . Valdebenito‐Maturana et al carried out a spatial expression analysis of transposable elements (TEs), developed SpatialTE tools, and applied them to the spinal cord data of ALS‐infected mice 95 . Interestingly, the expression of TEs in the dorsal and ventral horns was higher than that observed in the medial or distal regions of the spinal cord.…”

Section: Application Of Spatial Transcriptomics (St) In Scimentioning

confidence: 99%

Single‐cell RNA sequencing for traumatic spinal cord injury

Cao

Zhu

et al. 2022

The FASEB Journal

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Traumatic spinal cord injury (tSCI) is a severe injury of the central nervous system (CNS) with complicated pathological microenvironment that results in hemorrhage, inflammation, and scar formation. The microenvironment of the injured spinal cord comprises heterogeneous neurons, glial cells, inflammatory cells, and stroma-related cells. Increasing evidence has indicated that the altered cellular and molecular microenvironment following tSCI is a key factor impeding functional recovery. Single-cell RNA sequencing (scRNA-seq) has provided deep insights into the dynamic cellular and molecular changes in the microenvironment by comprehensively characterizing the diversity of spinal cord cell types. Specifically, scRNA-seq enables the exploration of the molecular mechanisms underlying tSCI by elucidating intercellular communication in spinal cord samples between normal and injury conditions at a single-cell resolution. Here, we first described the pathological and physiological processes after tSCI and gave a brief introduction of the scRNA-seq technology. We then focused on the recent scRNA-seq researches in tSCI, which characterized diverse cell-type populations and specific cell-cell interactions in tSCI. In addition, we also highlighted some potential directions for the research of scRNA-seq in tSCI in the future.

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Spatially Resolved Expression of Transposable Elements in Disease and Somatic Tissue with SpatialTE

Cited by 6 publications

References 30 publications

Activation of Transposable Elements in Human Skeletal Muscle Fibers upon Statin Treatment

Activation of Transposable Elements in Human Skeletal Muscle Fibers upon Statin Treatment

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

Single‐cell RNA sequencing for traumatic spinal cord injury

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