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

Vitor Ikeda Ito-Silva

1,*

Lícia C Silva-Costa

Sintia Iole Belangero

2,3

Bradley Joseph Smith

1,*

Daniel Martins-de-Souza

1,4,5,6,*

Affiliation +

*Correspondence to: Vitor Ikeda Ito-Silva, Department of Biochemistry, Laboratory of Neuroproteomics, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-862, Brazil. E-mail: v195227@dac.unicamp.br
Bradley Joseph Smith, Department of Biochemistry, Laboratory of Neuroproteomics, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-862, Brazil. E-mail: smith.unicamp@gmail.com
Daniel Martins-de-Souza, Department of Biochemistry, Laboratory of Neuroproteomics, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-862, Brazil; Experimental Medicine Research Cluster (EMRC), Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-887, Brazil; D’Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ 22281-100, Brazil; INCT in Modelling Human Complex Diseases With 3D Platforms (Model3D), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasília, DF 70830-010, Brazil. E-mail: dmsouza@unicamp.br

EXO. 2026;1:202618. 10.70401/EXO.2026.0019

Received: May 16, 2026Accepted: August 14, 2026Published: August 14, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

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.

Keywords

Brain, psychiatry, multi-omics, single-cell, translational omics

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Ito-Silva VI, Silva-Costa LC, Belangero SI, Smith BJ, Martins-de-Souza D. Single-cell and spatial multi-omics for mapping the brain across molecular layers. EXO. 2026;1:202618. https://doi.org/10.70401/EXO.2026.0019

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EXO - Beyond the Cell

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

Vitor Ikeda Ito-Silva

Lícia C Silva-Costa

Sintia Iole Belangero

Bradley Joseph Smith

Daniel Martins-de-Souza

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

Vitor Ikeda Ito-Silva

Lícia C Silva-Costa

Sintia Iole Belangero

Bradley Joseph Smith

Daniel Martins-de-Souza

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