Biology subjects

van Dis, V.

Publications and source records attributed to van Dis, V..

3 recordsLinked to original sources

bioRxiv2026

Behavior-coupled single-cell transcriptomics reveals trafficking protein-dependent regulation of tumor cell migration

Aggressive cellular migration underlies cancer invasion and metastatic dissemination, yet the molecular programs defining highly migratory tumor cell states remain poorly characterized. In head and neck squamous cell carcinoma (HNSCC), metastatic progression is associated with poor clinical outcome, motivating method developments that link migratory behavior to underlying mechanisms. Here, we present behavior-coupled single-cell sequencing (BC-seq), a live-cell imaging-guided transcriptomic platform that enables real-time identification, isolation, and profiling of individual cells based on migratory behavior. Applying BC-seq to 10 HPV-negative oral squamous cell carcinoma (OSCC), the most common HNSCC subtype, we distinguished fast-migrating cells (FMCs) from slow-migrating cells (SMCs) and identified transcriptional programs associated with aggressive migration. Mechanistically, BC-seq uncovered cholesterol-regulated signaling pathways and associated trafficking proteins involving SREBP2, STARD4, Cavin1/3, and VEGFR2 that promotes actin cytoskeletal remodeling and cellular motility. Disruption of STARD4-mediated cholesterol trafficking or Cavin1/3-dependent VEGFR2 nuclear translocation significantly impaired cell migration, linking cholesterol metabolism to migratory machinery. We next examined whether molecular programs associated with aggressive migration are reflected in clinical outcomes. A 15-gene expression signature derived from FMCs predicted distant metastasis with 83.6% accuracy in an independent OSCC cohort, outperforming conventional clinicopathological risk stratification. Together, our study establishes BC-seq as an approach for integrating dynamic cellular behavior with single-cell transcriptomics to uncover mechanisms of aggressive migration and clinically relevant molecular signatures.

cancer biology↗

bioRxiv2025

Spatial Transcriptomics of Schizophrenia Insular Cortex Reveals Blood-Brain Barrier Hyperglycolysis and Increased Parenchymal Mitochondrial Respiration

IntroductionThe blood-brain barrier (BBB) acts as the metabolic and immunological gatekeeper of the brain. Since alterations in neurometabolism and neuroimmunity are found in schizophrenia-spectrum disorders (SSD) which are hypothesised to be important disease mechanisms, we aimed to investigate whether changes in BBB function could underly these findings using a novel spatially resolved transcriptomics technique. MethodsFormalin-fixed paraffin-embedded insular cortex tissue from 8 brain donors with SSD and 8 matched controls derived from the Netherlands Brain Bank-Psychiatry were selected for whole transcriptome analysis (GeoMx Human Whole Transcriptome Atlas) on the GeoMx Digital Spatial Profiler platform. Combining nuclear staining with an endothelial cell marker (CD31) allowed for the separation of BBB and parenchyma areas of interest (AOIs) for downstream sequencing on the Illumina NextSeq 2000. For each sample, biological triplicates were sequenced. Comparing SSD to control for both the BBB and parenchyma AOIs, differentially expressed genes (DEGs) were identified using a Linear Mixed Model, a heatmap was created displaying all genes with a false-discovery rate <0.01, and Fast Gene Set Enrichment Analysis was used for pathway analysis. ResultsA total of 96 whole transcriptome profiles were generated (24 BBB and 24 parenchyma for both SSD and controls). Expression of endothelial genes (PECAM1/CD31, CLDN5, VWF, CD34, ENG) was significantly increased in BBB, confirming enrichment of endothelial cells (ECs) in this AOI. Cluster analysis showed perfect clustering of BBB versus parenchyma, and good clustering of SSD samples within the BBB cluster. At a |Log2FC| [≥] 0.25, we identify 265 significantly DEGs in the BBB AOI and 6 in the parenchyma AOI comparing SSD to control. Pathway analysis revealed a distinct metabolic transcriptional profile in SSD, characterized by hyperglycolysis in the BBB and increased mitochondrial energy metabolism in parenchyma. ConclusionOur findings implicate the BBB in the metabolic pathophysiology of SSD. Furthermore, our findings add nuance to the existing understanding of brain bioenergetic alterations in SSD, suggesting that metabolic changes may be region-specific rather than generalized. This highlights the need for a brain mapping approach examining multiple brain regions from the same donor. Finally, the distinct metabolic profiles of the BBB and brain parenchyma emphasize the importance of spatial multi-omics in post-mortem psychiatric research and the potential for therapies targeting BBB function in SSD.

neuroscience↗

bioRxiv2021

No evidence for aberrant expression of amyloid β and phosphorylated tau proteins in herpes simplex virus-infected human neurons in vivo

Increasing evidence implicates the neurotropic herpes simplex virus 1 (HSV-1) in the pathogenesis of Alzheimers Disease (AD). However, it is unclear whether previously reported findings in HSV-1 cell culture and animal models can be translated to humans. Here, we analyzed clinical specimens from latently HSV-1 infected individuals and individuals with lytic HSV infection of the brain (herpes simplex encephalitis; HSE). Latent HSV-1 DNA load in trigeminal ganglia was identical between AD patients and controls, and latently HSV-infected neurons did not express amyloid {beta} (A{beta}) or hyperphosphorylated tau (pTau). Some HSE patient brains presented with ageing-related intraneuronal A{beta} accumulations, neurofibrillary tangles (NFT) or extracellular A{beta} plaques, but these were neither restricted to HSV-infected neurons nor brain regions containing virus-infected cells. Analysis of unique brain material from an AD patient with concurrent HSE showed that HSV-infected cells frequently localized close to A{beta} plaques and NFT, but did not exacerbate AD-related pathology in relation to HSV infection. HSE-associated neuroinflammation was not associated with specific A{beta} or pTau phenotypes. Collectively, the data indicate that neither latent nor lytic HSV infection of human neurons in vivo is directly associated with aberrant A{beta} or pTau protein expression.

microbiology↗