INTRODUCTION: Advanced transcriptomic technologies are essential for unraveling gene expression complexity and offer powerful tools for studying biological systems and disease mechanisms. These methods are increasingly central to both basic and translational neuroscience.

AIM(S): This poster highlights how bulk, single-cell, and spatial transcriptomic technologies have been applied in preclinical and disease-modeling studies supported by GeneCore, an academic facility specializing in advanced transcriptomics. We aim to demonstrate how these approaches advance understanding of disease mechanisms and therapeutic strategies.

METHOD(S): Bulk RNA sequencing was used to study responses to delayed C3a treatment in a photothrombotic mouse stroke model. Single-cell RNA sequencing characterized early pathology in in vitro models of Alexander disease. Spatial transcriptomics mapped glial responses in a permanent ischemia model. We also summarize efforts to standardize small RNA analysis protocols.

RESULTS: Bulk transcriptomic profiling revealed that delayed C3a treatment suppresses astrocyte inflammatory responses in the peri-infarct cortex and upregulates genes involved in synaptic function. Single-cell analysis identified aberrant neurodevelopment in human iPSC-derived models of Alexander disease, suggesting a potential novel disease mechanism. Spatial transcriptomics captured region-specific and time-dependent glial responses, offering insights into molecular and cellular dynamics during recovery. Although technically demanding, small RNA profiling is a feasible approach for system-level or targeted characterization of regulatory miRNA networks.

CONCLUSIONS: The integration of bulk, single-cell, and spatial transcriptomic approaches enables comprehensive analysis of gene expression programs, cellular diversity, and tissue organization. Together, these technologies provide actionable insights into neurological disease mechanisms and support the development of targeted therapeutic strategies.