Biology subjects

Lillo, S.

Publications and source records attributed to Lillo, S..

4 recordsLinked to original sources

bioRxiv2026

TileScope quantifies spatial gene expression relationships beyond colocalization

Gene expression patterns within the same tissue region can exhibit similar correlation or enrichment, but still differ in their organization within regions and at their boundaries. We present TileScope, a framework for analysing genes and transcriptional programs within predefined tissue regions, their components and their contacts with neighbouring regions. TileScope combines regional enrichment, within-region correlation, cross-correlation over distance and expression differences near specific boundaries. Repeated spatial partitions and consensus aggregation show how these measurements depend on the grouping of spots or cells. Across 30 controlled constructions derived from glioblastoma and hepatocellular carcinoma data representing ten spatial expression scenarios, combined measurements separated arrangements that individual statistics left ambiguous, including coincident patches, gradients and expression localised at region boundaries. In 30 human glioblastoma sections, TileScope distinguished shared regional enrichment from internal covariation and identified hypoxia-associated expression localised at region boundary despite negligible within-region correlation. In newly acquired Visium profiles of control and myeloid-targeted MCT1-knockout (KO) orthotopic GL261 mouse gliomas, proliferation and myeloid programs were enriched in tumour peripheries but showed opposite within-periphery-region correlations. Proliferation was higher near the tumour-facing boundary in both samples, whereas myeloid expression was higher near the tumour-facing boundary in the control and farther within periphery in the KO condition. Xenium applications on glioblastoma and breast cancer samples demonstrated feasibility with irregularly spaced individual cells and different regional annotations. TileScope provides spatially explicit descriptions of gene and program relationships, linking their organization within tissue compartments to their sensitivity to aggregation.

bioinformatics↗

bioRxiv2026

SpacePath enables pathway and molecular-family analysis beyond annotation ambiguity in spatial metabolomics and lipidomics

Mass spectrometry imaging (MSI) maps metabolites and lipids in tissue with spatial resolution, but molecular identity remains partly resolved: single ions match multiple candidate compounds, and most detected metabolites and lipids fall outside canonical biochemical pathways. We developed SpacePath, a computational framework that retains ion-to-compound ambiguity, scores canonical pathways across tissue locations, and groups assignments that were unmapped to pathways into de novo molecular families by chemical similarity. Pathway mappings covered on average only 1% of molecular assignments, whereas the combined SpacePath representation covered 24% of pooled assignments. Benchmarking on four public spatial lipidomics datasets (healthy mouse brain, cerebellum, a demyelination model, and human bladder cancer) recovered previously reported spatial patterns. In newly acquired glioblastoma xenograft datasets, SpacePath identified lipid programs specific to tumor and surrounding brain, and SpiderMass-MS/MS independently confirmed four tumor-associated features from a de novo family, refining the initial MS1 assignments. SpacePath extends the spatial interpretation of MSI data beyond canonical pathways while preserving annotation uncertainty.

bioinformatics↗

bioRxiv2026

A Female-Specific Microglial Redox Program Gates Susceptibility to Obesity

Chronic consumption of energy-dense, high-fat foods persistently exposes hypothalamic circuits that govern body weight to nutrient excess, progressively altering their activity and thereby promoting obesity. Microglia, the brain resident immune cells, sense circulating lipids, but how their intracellular metabolic programs adapt to chronic dietary excess, and how this contributes to obesity risk, is unclear. Here, we reveal a sex-dependent control of calorie overload by hypothalamic microglial cells. In females, but not males, microglia engage a protective metabolic program with increased antioxidant capacity and mitochondrial network remodeling, conferring resistance to early weight gain. Over time, activation of mTORC1 signaling in microglia disrupts mitochondrial functions and dismantles this transient resilience, culminating in weight gain. These findings identify microglial mTORC1 as a sex-specific switch between resilience and vulnerability to obesity and position microglial metabolism as a tractable target for sex-informed weight control.

neuroscience↗

bioRxiv2026

Microbiota-gut-brain axis modulation drives glioblastoma progression and therapy resistance

Glioblastoma is a highly aggressive brain tumour with poor prognosis, whose aetiology, progression, and therapeutic resistance remain incompletely understood. While the microbiota-gut-brain axis has emerged as a key regulator of neurological disorders, its role in glioblastoma biology and treatment response is still largely unexplored. Using a clinically relevant immunocompetent murine model combining glioblastoma stem cell implantation, dextran sodium sulfate-induced gut inflammation, and a full Stupp-like therapeutic protocol, we investigated bidirectional gut-brain communication in glioblastoma. Tumour growth and recurrence were monitored by bioluminescence imaging, tumour transcriptomic profiles were analysed by RNA sequencing, and brain and colon tissues were subjected to histological and molecular analyses. Gut microbiota composition was assessed by 16S rRNA sequencing, while systemic metabolites and cytokines were quantified in plasma. Cross-compartment association bioinformatic analyses were performed to correlate multi-organ readouts. Gut inflammation enhanced glioblastoma growth and promoted tumour recurrence following therapy. Tumour progression was associated with increased infiltration of immunosuppressive macrophages, whereas recurrence correlated with elevated oxidative DNA damage. Remarkably, glioblastoma exerted systemic immunomodulatory effects, attenuating intestinal and systemic inflammatory responses, and induced profound remodelling of gut microbiota composition and predicted metabolic function, including enrichment of Akkermansia and depletion of Lactobacillus. Systemic metabolic profiling was investigated as a route of communication within the gut-brain axis and revealed adaptations in DSS-treated mice associated with tumour burden and therapeutic response. Multi-compartment correlation and multivariable association analyses identified specific bacterial genera and circulating metabolites associated with tumour volume, intestinal inflammation, and genomic instability. These findings uncover a dynamic, bidirectional microbiota-gut-brain axis in glioblastoma and identify intestinal inflammation as a critical determinant of tumour progression and therapeutic outcome. Targeting gut disturbances and microbiota-associated metabolic pathways may represent novel strategies to modulate glioblastoma aggressiveness and treatment response.

cancer biology↗