SMA’s effects on gene activity vary across tissues: Study
Researchers identify few consistently dysregulated genes, pathways
The activity of many genes may be dysregulated in spinal muscular atrophy (SMA), but the way the disease affects genes seems to vary across different types of tissues in the body, a study found.
“Our comparative meta-analysis identified only few genes and pathways that were consistently dysregulated in SMA across different tissues and experimental settings,” the researchers wrote. “Conversely, many genes and pathways appeared to play a tissue-specific role in SMA.”
The study, “Comparative meta-analysis of transcriptomic studies in spinal muscular atrophy: comparison between tissues and mouse models,” was published in BMC Medical Genomics.
SMA is chiefly caused by mutations in the gene SMN1. Several studies have found that SMA results in alterations of the transcriptome, the overall landscape of gene activity in cells, leading some genes to be overactive while others are underactive.
Although individual studies have provided some useful insights, they have often looked at different types of tissue with different methodologies. In addition, some studies have used human tissue while others have used mouse models.
Search for consistency in gene activity
Scientists in Germany compared and contrasted transcriptome datasets from six previous studies. Their goal was to see whether differences in gene activity are consistent among different tissues and types of studies.
“While individual transcriptomic studies provide insights under specific experimental settings, the aim of this work is to systematically re-analyse publicly available gene expression data of a selection of these studies to better understand the differences in the transcriptome under different settings such as different organs and mouse models,” the researchers wrote.
Results showed a lot of variability. In some comparisons, as the number of genes with altered activity levels, or expression, ranged from zero to 1,655 across the studies. The largest effects, meaning the largest portion of differentially expressed genes, were found in the skeletal muscle that enables movement and in motor neurons — the specialized nerve cells that control movement — derived from stem cells.
“Overall, we could identify only small similarities between the results from the individual studies,” the researchers wrote, noting that these differences may “be related to the different study settings such as mouse strains, types of organs and time points.”
The researchers highlighted a few genes that were consistently identified in many of the analyses. For example, Mt2, a gene that helps cells respond to oxidative damage, was overactive in many of the transcriptome comparisons. The Mt2 gene has been shown to have nerve-protecting properties, “which in turn is important in the maintenance of neuronal function and integrity in neurodegenerative diseases including SMA,” the scientists wrote.
Another gene, Snrpa1, was upregulated in the spinal cord. Snrpa1Â is involved in pre-messenger RNA splicing, a key process to produce a mature messenger RNA molecule that serves as an intermediary between genes and new proteins.
Beyond individual genes, the researchers said, the big takeaway from this analysis is that the way SMA affects genetic activity in cells likely varies by tissue type and across different scientific models.
“We avoided to over-interpret the results and are aware that the studies included, here, have very small sample sizes,” the scientists concluded. “This summary of six transcriptomic studies can therefore not be seen as a proof of facts, but may help to further support findings of future … studies on SMA.”
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