analysis-based-on-tcga-data-single-cell-data-taking-trpm4-as-an

Analysis Based on TCGA Data and Single-cell Data, taking <em>TRPM4</em> as an Example

In this article, an analysis method is introduced based on public transcriptomic datasets and single-cell datasets, which could be used to comprehensively ...

transcriptomic-analysis-based-on-bulk-rna-seq-data

Transcriptomic Analysis Based on Bulk RNA-seq Data

Nonalcoholic fatty liver (NAFL) is usually considered a benign condition; however, once it progresses to non-alcoholic steatohepatitis (NASH), patients ...

The First Affiliated Hospital with Nanjing Medical University

The First Affiliated Hospital of Nanjing Medical University

There is increasing interest in developing therapeutic interventions aimed at preventing neuroinflammation in Parkinson's disease (PD). However, the specific characteristics of inflammation across different cell types and the underlying mechanisms of PD-related inflammation remain inadequately understood. In this study, we conducted an analysis of single-cell RNA sequencing (scRNA-seq) and microarray data derived from human PD midbrain tissue, specifically focusing on the substantia nigra compacta (SNc). These datasets were sourced from the (GEO) database. We utilized GSVA, GSEA, as well as KEGG and GO analyses to explore transcriptional variations associated with PD. Furthermore, trajectory and SCENIC analyses were conducted to uncover the mechanisms underlying PD progression. Subsequent animal and cellular experiments validated the role of the regulon in regulating neuroinflammation. Results: Our analysis revealed that microglia displayed the highest levels of inflammatory activity, characterized by an increased abundance of microglia in the proinflammatory activated state within the midbrain and SNc of PD patients. This finding was further validated in a PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The transcription factor STAT3 demonstrated significant upregulation and was implicated in promoting the inflammatory response and activating microglia within the PD context. In the 1-methyl-4-phenylpyridine (MPP +)-induced BV2 cell model, inhibition of STAT3 led to reduced levels of inflammation, hindered STAT3 phosphorylation, and decreased the production of inflammatory factors. Furthermore, the downregulation of P-STAT3 alleviated the harmful effects on SH-SY5Y cells that were cocultured in the conditioned medium. Conclusions: Our study underscored the pivotal role of the transcription factor STAT3 as a central regulator of proinflammatory activation in microglia within PD. These findings offer fresh insights into PD pathogenesis and suggest potential avenues for the development of novel therapeutic strategies.

Integrated Analysis of Single-Cell and Transcriptome Data Reveals the Role and Regulatory Mechanisms of Neuroinflammation in Parkinson's Disease.

The pathophysiological mechanisms underlying cerebral ischemia-reperfusion (I/R) injury are highly complex. Previous studies have indicated phenotypic changes in various cell types following stroke but have failed to identify the key regulatory genes and cell subtypes associated with the disease. The study utilized five datasets: GSE227651, GSE104036, GSE116878, GSE249957, and GSE22255. The Seurat pipeline was employed for standard quality control and single-cell data analysis. Monocle2 and CytoTRACE were used for trajectory analysis, while Mfuzz was applied to identify time-series gene expression patterns. Middle cerebral artery occlusion (MCAO) mice served as the animal model for cerebral I/R injury, and oxygen-glucose deprivation/reoxygenation (OGD/R)-treated BV2 cells were used to simulate microglial phenotypic changes following ischemia-reperfusion. qPCR, Western blotting, and immunofluorescence staining were used to detect key gene and protein alterations. P65 was identified as a key transcription factor driving inflammatory responses and transcriptional changes following ischemic stroke. Two microglial subtypes, Cx3cr1 + and Cdk1+, were identified, with their proportions significantly increasing on days 1 and 3 after MCAO. Increased levels of inflammation, neuronal apoptosis, and P65 phosphorylation in microglia were observed in both the MCAO animal model and OGD/R cell model. Notably, inhibition of P65 phosphorylation effectively suppressed the progression of inflammation during cerebral I/R injury. We identified microglial subtypes associated with inflammatory responses following cerebral ischemia-reperfusion injury, with their proportions increasing post-injury. P65 was confirmed as a critical regulator of the inflammatory response, contributing to neuronal protection and the restoration of neurological function.

Single-cell sequencing and transcriptomic data reveal that P65 activation significantly promotes microglia-mediated neuroinflammation after ischemic stroke.

BackgroundMicroglia are central mediators of neuroinflammation in Alzheimer's disease (AD), contributing significantly to disease pathogenesis. Understanding microglial heterogeneity and their regulatory mechanisms is critical for identifying potential therapeutic targets.ObjectiveThis study aimed to investigate the diversity of microglial subpopulations in AD and uncover key transcriptional regulators driving their pathogenic activity.MethodsWe integrated bulk RNA sequencing data from AD patients and 5×FAD mouse models with single-cell RNA sequencing (scRNA-seq) to profile microglial heterogeneity. Differential gene expression, pathway enrichment, pseudotime trajectory, and SCENIC analyses were used to identify functionally distinct subsets and regulatory networks. Experimental validation was conducted through in vivo assays in 5×FAD mice and in vitro inhibition studies targeting HIF-1α.ResultsA unique microglial subpopulation, termed microglia_2, was identified with an inflammatory-angiogenic transcriptional signature that was enriched during AD progression. This subset showed significant activation of inflammatory pathways. Pseudotime and SCENIC analyses revealed HIF-1α as a master regulator of microglia_2. In 5×FAD mice, cognitive decline was accompanied by increased expression of HIF-1α and Apoe, as well as microglial activation in the prefrontal cortex. In vitro inhibition of HIF-1α significantly reduced microglial inflammation.ConclusionsOur study demonstrates that a specific microglial subpopulation characterized by elevated HIF-1α expression may contribute to AD-associated neuroinflammation. By integrating transcriptomic analyses and experimental validation, we provide cell type-specific insights into disease mechanisms, offering potential insights for future mechanistic studies and therapeutic exploration.

HIF-1α-induced microglia-mediated neuroinflammation is involved in Alzheimer's disease: Evidence from single-cell transcriptomic analysis.

Freezing of gait (FOG) is a common gait disorder in the advanced stages of Parkinson's disease (PD), closely associated with impaired balance and executive function. This study aimed to investigate specific changes in brain glucose metabolism in FOG patients using F-FDG PET. Deep learning methods were utilized to offer valuable perspectives for identifying FOG.

Characteristics of brain glucose metabolism in Parkinson's disease patients with freezing of gait: a study based on F-FDG PET imaging and deep learning.

Bladder cancer (BLCA) is one of the most invasive and malignant tumors in the world, thus leading to the urgent need of an accurate and recognizable biomarker. Several previous research has shown that Transient Receptor Potential Melastatin 4 (TRPM4) plays an important role in measuring vascular fragility and endothelial function. However, the role of TRPM4 in tumor hasn't been explored.

Transient Receptor Potential Melastatin 4 (TRPM4) is associated with an immuno-stimulatory TME and better prognosis in BLCA.

Noninvasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can induce long-term potentiation-like facilitation, but whether the combination of TMS and tDCS has additive effects is unclear. To address this issue, in this randomized crossover study, we investigated the effect of preconditioning with cathodal high-definition (HD) tDCS on intermittent theta burst stimulation- (iTBS-) induced plasticity in the left motor cortex. A total of 24 healthy volunteers received preconditioning with cathodal HD-tDCS or sham intervention prior to iTBS in a random order with a washout period of 1 week. The amplitude of motor evoked potentials (MEPs) was measured at baseline and at several time points (5, 10, 15, and 30 min) after iTBS to determine the effects of the intervention on cortical plasticity. Preconditioning with cathodal HD-tDCS followed by iTBS showed a greater increase in MEP amplitude than sham cathodal HD-tDCS preconditioning and iTBS at each time postintervention point, with longer-lasting after-effects on cortical excitability. These results demonstrate that preintervention with cathodal HD-tDCS primes the motor cortex for long-term potentiation induced by iTBS and is a potential strategy for improving the clinical outcome to guide therapeutic decisions.

Preconditioning with Cathodal High-Definition Transcranial Direct Current Stimulation Sensitizes the Primary Motor Cortex to Subsequent Intermittent Theta Burst Stimulation.

To investigate whether anodal high-definition transcranial current stimulation (HD-tDCS) over the left dorsolateral pre-frontal cortex (DLPFC) could modulate the heart rate (HR) and heart-rate variability (HRV) in healthy young people.

Anodal high-definition transcranial direct current stimulation reduces heart rate and modulates heart-rate variability in healthy young people: A randomized cross-controlled trial.

Despite the significant frequency of autonomic dysfunction (AutD) in Parkinson's disease (PD) patients, its pathogenesis and diagnosis are challenging. Here, we aimed to further explore the mechanism of phosphorylated α-synuclein (p-α-syn) deposited in vagus nerve Schwann cells (SCs) causing SCs damage and PD AutD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was administrated to C57BL/6 mice twice a week for 35 days. Following the final injection, locomotor functions, gastrointestinal symptoms, urine functions, and cardiovascular system functions were evaluated. Meanwhile, we examined p-α-syn deposited in vagus nerve SCs, Toll-like receptor 2 (TLR2) activation, and SCs loss using immunofluorescence, western blot, and Luxol fast blue staining. In vitro, the rat SCs line RSC96 cells were exposed to α-synuclein preformed fibril (α-syn PFF), and cell viability was detected by CCK8. Co-IP was used to identify the interaction between p-α-syn and TLR2. Furthermore, the role of TLR2 in p-α-syn-mediated SCs damage was confirmed by the administration of CU-CPT22, a specific blocker of TLR2. In vivo, apart from dyskinesia, MPTP mice exhibited constipation, urinary dysfunction, and cardiovascular failure, which were associated with the deposition of p-α-syn in vagus nerve SCs, TLR2 activation, and vagus nerve demyelination. In vitro, stimulation of α-syn PFF induced a time-dependent loss of viability, and p-α-syn deposited in RSC96 cells induced a cellular inflammatory response by interacting with TLR2, resulting in cell dysfunction and apoptosis. However, both SCs inflammatory response and cell viability were alleviated after inhibition of TLR2. Furthermore, 1 h fecal pellets and water content, the frequency of 1 h urine, blood pressure, heart rate, and heart rate variability of mice in the MPTP + CU-CPT22 group were also improved. Our results support the perspective that p-α-syn interacts with TLR2 induced SCs damage and is involved in PD AutD, which sheds fresh light on the mechanism of PD AutD and indicates a promising treatment for PD AutD targeting SCs p-α-syn/ TLR2 signaling pathway.

Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson's disease autonomic dysfunction.

ArticleTotal : 2	Year
Publication title	2025
Publication title	2026

Article	Year
Integrated Analysis of Single-Cell and Transcriptome Data Reveals the Role and Regulatory Mechanisms of Neuroinflammation in Parkinson's Disease. Inflammation\| PubMed ID: 40285838	2025
Single-cell sequencing and transcriptomic data reveal that P65 activation significantly promotes microglia-mediated neuroinflammation after ischemic stroke. Scientific reports\| PubMed ID: 40404711	2025
HIF-1α-induced microglia-mediated neuroinflammation is involved in Alzheimer's disease: Evidence from single-cell transcriptomic analysis. Journal of Alzheimer's disease : JAD\| PubMed ID: 40971318	2025
Characteristics of brain glucose metabolism in Parkinson's disease patients with freezing of gait: a study based on F-FDG PET imaging and deep learning. BMC neurology\| PubMed ID: 41174540	2025
Transient Receptor Potential Melastatin 4 (TRPM4) is associated with an immuno-stimulatory TME and better prognosis in BLCA. Discover oncology\| PubMed ID: 41266683	2025
Preconditioning with Cathodal High-Definition Transcranial Direct Current Stimulation Sensitizes the Primary Motor Cortex to Subsequent Intermittent Theta Burst Stimulation. Neural plasticity\| PubMed ID: 34721571	2021
Anodal high-definition transcranial direct current stimulation reduces heart rate and modulates heart-rate variability in healthy young people: A randomized cross-controlled trial. Frontiers in cardiovascular medicine\| PubMed ID: 36531710	2022
Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson's disease autonomic dysfunction. Cell death discovery\| PubMed ID: 38278799	2024

Yao Geng

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