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Infernape uncovers cell type–specific and spatially resolved alternative polyadenylation in the brain

2023; Cold Spring Harbor Laboratory Press; Volume: 33; Issue: 10 Linguagem: Inglês

10.1101/gr.277864.123

1549-5469

Bowei Kang, Yalan Yang, Kaining Hu, Xiangbin Ruan, Yilin Liu, Pinky Lee, Jasper Lee, Jingshu Wang, Xiaochang Zhang,

Cancer-related gene regulation

Differential polyadenylation sites (PAs) critically regulate gene expression, but their cell type-specific usage and spatial distribution in the brain have not been systematically characterized. Here, we present Infernape, which infers and quantifies PA usage from single-cell and spatial transcriptomic data and show its application in the mouse brain. Infernape uncovers alternative intronic PAs and 3'-UTR lengthening during cortical neurogenesis. Progenitor-neuron comparisons in the excitatory and inhibitory neuron lineages show overlapping PA changes in embryonic brains, suggesting that the neural proliferation-differentiation axis plays a prominent role. In the adult mouse brain, we uncover cell type-specific PAs and visualize such events using spatial transcriptomic data. Over two dozen neurodevelopmental disorder-associated genes such as Csnk2a1 and Mecp2 show differential PAs during brain development. This study presents Infernape to identify PAs from scRNA-seq and spatial data, and highlights the role of alternative PAs in neuronal gene regulation.