Single-cell and spatial multi-omics for mapping the brain across molecular layers

Abstract

Understanding how molecular mechanisms occur and shape brain function and dysfunction remains a central challenge in neuroscience. Although bulk omics methods have contributed significantly to the field, they fail to address the cellular and spatial heterogeneity of the brain. Single-cell and spatial multi-omics approaches emerged to address these limitations by enabling integrated, high-resolution profiling of molecular layers while preserving cellular and tissue context. However, despite their impact on basic neuroscience, the clinical translation of these methods remains limited by cost, technical complexity, and analytical challenges. In this review, we summarize recent advances in single-cell and spatial multi-omics applied to brain research, critically evaluating their technological capabilities, translational potential, and current limitations. We further highlight emerging directions, including spatiotemporal integration, morphomics, improved reproducibility, and the expansion of multi-omics research to biologically and environmentally diverse populations.