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Review
. 2025 Aug 12:S0168-9525(25)00161-1.
doi: 10.1016/j.tig.2025.06.010. Online ahead of print.

Unraveling brain complexity: from single-cell to spatial m6A technologies

Affiliations
Review

Unraveling brain complexity: from single-cell to spatial m6A technologies

Shuangshuang Feng et al. Trends Genet. .

Abstract

The brain's complexity arises from diverse cell types varying spatially and temporally. N6-methyladenosine (m6A), the most abundant mRNA modification, regulates gene expression and cellular function. While bulk sequencing studies have provided foundational insights, they obscure m6A heterogeneity across cell types and brain regions. Recent advances in single-cell and spatial m6A detection technologies have revolutionized our understanding, enabling the exploration of cell-type-specific and spatial m6A landscapes. This review discusses the limitations of bulk approaches and highlights emerging single-cell and spatial technologies. We also provide a forward-looking perspective on how technological improvements can further uncover m6A's role in brain complexity, offering new opportunities to develop targeted therapies for cell-type-specific m6A-marked RNAs.

Keywords: N(6)-methyladenosine (m(6)A); Oxford Nanopore sequencing; brain heterogeneity; single-cell sequencing; spatial transcriptomics.

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Conflict of interest statement

Declaration of interests M.J.K. is an Associate Editor for Oxford Open Neuroscience. F.S. declares no competing interests.

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