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

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.