Next-Generation Methodologies in Neurogenomics: Leveraging Spatial and Single-Cell RNA Sequencing

The central nervous system (CNS) is characterized by remarkable cellular diversity and spatial organization, both of which are critical to brain function and highly relevant to the progression of neurological disorders. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, ALS, and MS involve complex, multicellular interactions that single-cell and spatial transcriptomics can help unravel by investigating gene expression patterns at the level of individual cell types and their spatial organization within tissues.

Next-generation sequencing (NGS) technologies—particularly single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics—are enabling researchers to dissect these complexities at an unprecedented resolution. These methods are reshaping our understanding of cell-type-specific contributions to disease, regional vulnerability, and the molecular mechanisms that drive neurodegeneration.

Defining Cell Identity and State with Single-Cell Sequencing

scRNA-seq allows transcriptomic profiling at the resolution of individual cells, making it possible to capture rare cell populations, track dynamic cellular responses, and uncover cell-state transitions over time.

Applications in Neuroscience

• Characterizing transcriptional changes in specific neuronal and glial subtypes across disease stages

• Identifying reactive or disease-associated microglia and astrocytes, which may play active roles in neurodegeneration

• Resolving cellular heterogeneity within affected regions, enabling stratification of neuronal vulnerability

Recent studies have leveraged scRNA-seq to uncover disease-associated microglial phenotypes in Alzheimer’s models, and profile region-specific neuron loss in Parkinson’s disease. These discoveries laid the groundwork for novel therapeutic strategies targeting cell-type-specific dysfunction.

Preserving Regional and Microenvironmental Context with Spatial Transcriptomics

While single-cell data enables high-resolution characterization of gene expression, spatial transcriptomics retains the tissue architecture, allowing researchers to localize transcriptional changes to precise anatomical regions.

Applications in CNS Research

• Mapping the progression of neuropathology across cortical and subcortical regions

• Profiling spatially restricted molecular signatures associated with amyloid plaques, neurofibrillary tangles, or demyelinated lesions

• Understanding cell–cell and cell–matrix interactions within specific microenvironments

Spatial transcriptomic approaches have been instrumental in revealing early transcriptional alterations in Alzheimer’s-affected hippocampal subfields.

Integration of Modalities: A Systems-Level View of the Brain

The integration of single-cell and spatial transcriptomics provides a multidimensional framework for CNS research:

• Single-cell data identifies cellular phenotypes and transcriptional states

• Spatial data anchors these profiles within defined anatomical and pathological regions

• Combined, these data types enable reconstruction of cellular networks and spatial hierarchies relevant to disease pathogenesis

This integrative strategy is particularly powerful for modeling disease progression, identifying spatially constrained therapeutic targets, and elucidating the interplay between inflammation, neurodegeneration, and repair mechanisms.

Supporting High-Resolution Neurogenomic Research

Admera Health offers comprehensive NGS services that support CNS and neurological disorder research, including:

• Optimized single-cell RNA-seq workflows with customizable input requirements

• Spatial transcriptomic services compatible with fresh frozen or FFPE tissue

• Advanced bioinformatic analysis pipelines tailored to neuroscience applications

Our team supports researchers to help decode the molecular architecture of the brain—enabling precise insights into gene expression patterns with cutting-edge single-cell and spatial transcriptomics technologies coupled with our team of expert scientists and bioinformaticians. Learn more about single-cell sequencing applications and Admera’s capabilities in supporting single-cell discoveries.

Connect with an expert to learn more about how Admera Health can support your neuroscience research with single-cell analysis and high-resolution spatial transcriptomics.