Joglekar et al. (2024) present a comprehensive atlas of RNA isoforms in single cells from different brain regions, cell subtypes, and developmental stages in mice. Research has shown that the expression of full-length isoforms varies in 72% of genes, depending on cell type, brain region, and stage of development.
The authors found that splicing, early transcription and polyadenylation sites vary significantly between cell types, influencing protein architecture and associating with disease-linked genetic variation. In addition, genes involved in neurotransmitter transport and synapse renewal present variability between cell types in different anatomical regions.
The study also revealed that regulation of cell-type-specific splicing is pronounced in the adolescent transition, between days 21 and 28 after birth in mice. The regulation of the isoform during development is stronger than the regional regulation for the same cell type.
In conclusion, this detailed single-cell atlas of the regulation of full-length isoforms at different developmental stages and anatomical regions reveals a degree of variability of isoforms on multiple axes, with important implications for the understanding of brain function and development, as well as for the study of neurological diseases.
Refereencia:
JOGLEKAR, Anoushka et al. Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse and human brain. Nature Neuroscience, v. 27, pp. 1051–1063, 2024.
