Biology subjects

Truong, T. T. T.

Publications and source records attributed to Truong, T. T. T..

3 recordsLinked to original sources

bioRxiv2026

iPSC-Derived Myotubes from ME/CFS Patients Reveal Signature Genes, Isoforms and Pathways with Drug Repurposing Potential

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disorder. Its hallmark feature, post-exertional malaise (PEM), is a delayed and prolonged worsening of symptoms following even minor exertion. As PEM commonly includes muscle pain, weakness, exercise intolerance and impaired recovery, skeletal muscle dysfunction may contribute to its pathophysiology, but the underlying molecular processes remain poorly understood. We generated induced pluripotent stem cell-derived skeletal muscle myotubes from individuals with ME/CFS (n = 6) and healthy controls (n = 7) to investigate disease-associated transcriptomic alterations and identify potential therapeutic candidates. Myogenic progenitor cells from both groups differentiated into elongated, multinucleated myotubes expressing titin and myosin heavy chain, while qPCR profiling of myogenic differentiation markers further supported successful differentiation. Gene-level analysis identified three differentially expressed genes at an FDR-adjusted p < 0.05: ERVH48-1, CDX4 and SLC2A14. Isoform-switching analysis identified 16 genes with significant differential isoform usage, including CACNA1H, MIEF2, SMAD2 and CHD4. Gene set enrichment analysis identified broader pathway-level alterations involving RNA processing, protein synthesis, proteostasis, mitochondrial quality control, metabolism and muscle-related processes. Library of Integrated Network-based Cellular Signatures Phase 2 (LINCS2) analysis further prioritised 14 compounds associated with mitochondrial metabolism, glucose and lipid regulation, PPAR signalling, calcium and excitatory signalling, neuroimmune activity and cellular stress responses. Overall, ME/CFS iPSC-derived myotubes showed modest gene-level differences alongside broader isoform- and pathway-level alterations, supporting their use for investigating skeletal muscle biology and prioritising candidates for functional validation.

cell biology↗

bioRxiv2026

The toll-like receptor signalling pathway is altered in iPSC-derived cortical networks from people with bipolar disorder.

BackgroundInduced pluripotent stem cell (iPSC)-derived brain cells are widely utilized as in vitro models for several neuropsychiatric disorders, as they retain the donors genetic profile, offering a unique opportunity to study living human brain cells and perform controlled experimental manipulations. In this study, we conducted whole transcriptome sequencing of cortical networks (co-cultures of neurons and astrocytes) derived from 12 participants with bipolar disorder (BD) and 12 participants without a history of mental health disorders. We aimed to identify new molecular mechanisms underlying the pathophysiology of bipolar disorder. MethodsiPSCs were generated by reprogramming peripheral blood mononuclear cells using episomal vectors. They were then differentiated into neural progenitor cells and matured into cortical networks that express markers of neurons and astrocytes. Whole transcriptome data were obtained using the Illumina NovaSeq X sequencing platform. ResultsDifferential expression analysis was performed using DESeq2 in R, and the identified genes were used for gene set enrichment analysis, which identified 191 enriched pathways in BD. Of these, the toll-like signalling pathway, which is downregulated in BD, was further investigated. ConclusionOur results suggest a profound immune dysregulation in BD, particularly highlighting the immune systems role as a complex signalling network.

neuroscience↗

bioRxiv2025

Investigating the role of melatonin in bipolar disorder using transcriptomics

Melatonin may be a potential therapeutic target for bipolar disorder (BD) treatment; however, its role in BD pathophysiology remains poorly understood. This study aimed to investigate the therapeutic and mechanistic role of melatonin in BD using transcriptomics. RNA sequencing (RNAseq) data from 216 post-mortem dorsolateral prefrontal cortex samples (156 controls, 60 BD) were used to generate gene regulatory networks (GRNs). These were compared to lists of melatonin-related genes using gene set enrichment analysis (GSEA) to assess differential expression between people with BD and controls. Furthermore, RNAseq data from NT2-N cells treated with lithium, lamotrigine, valproate, or quetiapine were compared to lists of melatonin-related genes using GSEA. Finally, BD-associated gene regulatory patterns were compared to GRNs induced by melatoninergic agents to evaluate the repurposing potential of these pharmacotherapies for BD. Genes involved in inhibiting melatonin signalling were nominally upregulated in the BD post-mortem gene expression dataset. Transcription factors (TFs) activating melatonin signalling tended to be downregulated in BD females, while TFs inhibiting melatonin signalling were significantly downregulated in BD males. Regarding current treatments, quetiapine caused the greatest number of significant alterations in melatonin-related gene expression, followed by valproate, lithium, and then lamotrigine. Valproate was found to significantly upregulate genes involved in melatonin degradation. Finally, the melatonin receptor agonist GR-135531 was identified as a possible repurposing candidate for BD. Overall, this study provides new evidence that dysregulation of melatonin-related genes may play a role in the pathophysiology of BD, and suggests a number of melatoninergic agents as potential therapeutic candidates for BD.

molecular biology↗