Towards a comprehensive single-cell picture of RNA isoforms in mouse and human brain and their diseases

Most mammalian genes encode multiple distinct RNA isoforms and the brain harbors especially diverse isoforms. Complex tissue includes diverse cell types, which employ distinct isoforms. To untangle cell-type specific brain isoform profiles, we developed the first single-cell long-read technology for >>1,000 cells and fresh tissues (Single-cell isoform RNA sequencing - ScISOr-Seq [1]) as well as for frozen tissues (Single-nuclei isoform RNA sequencing - SnISOr-Seq [2]). To add spatial resolution, we developed Slide-isoform sequencing (Sl-ISO-Seq) [3]. We have mapped single-cell isoform expression across development, brain regions and species for the NIH Brain Initiative, and we have implemented highly accurate long-read interpretation software [4]. Finally, I will comment on further, yet unpublished, technologies of the lab.

1. Gupta*, Collier* et al, Nature Biotechnology, 2018
2. Hardwick*, Hu*, Joglekar* et al, Nature Biotechnology, 2022
3. Joglekar et al, Nature Communications, 2021
4. Prjibelski*, Mikheenko* et al, Nature Biotechnology, 2023

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