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Differential Expression Analysis of the SLIT Family in Different Brain Regions

ABSTRACT: The ageing human brain undergoes extensive remodelling of its extracellular matrix (ECM), yet the regional specificity and molecular drivers remain poorly defined. Here we combine bulk RNA-sequencing of post-mortem tissue (n = 63 across eight regions) with independent validation in the Genotype-Tissue Expression (GTEx) cohort (n = 962) to chart the expression landscape of the 239-member core matrisome. Hippocampus emerged as a major ECM outlier, with 114 matrisome genes—dominated by glycoproteins—up-regulated compared to the other seven regions (Fisher’s combined test, FDR < 0.05). Genes coding the axon-guidance ligands SLIT1, SLIT2 and SLIT3 ranked among the top hippocampal signatures and displayed strong co-expression with ROBO2 (r > 0.70). Age-stratified analysis in GTEx revealed a concerted decline of the SLIT-ROBO2 axis after 60y, aligning with hallmarks of cognitive ageing. Immunohistochemistry and western blotting (n = 3 per region) supported regional and subcellular patterns of SLITs ROBO2. These findings identify the SLIT-ROBO2 module as a hippocampus-centric, age-labile component of the human matrisome. We propose that sustained SLIT-ROBO signalling supports hippocampal synaptic plasticity, whereas its late-life attenuation may diminish structural resilience and heighten vulnerability to neurodegeneration. Our resource provides a framework for targeting ECM pathways to preserve brain connectivity during ageing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE311762 | GEO | 2026/03/01

REPOSITORIES: GEO

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