Authors
Hengxin Liu, Yanhong Hong, Yao Santo Zhang, Liyuan Xi, Huiying Yan, Yuxuan Liu, Qianqian Yang, Xing Sun, Shouliang Guan, Zan Chen, Yu Feng, Tao Zeng, Juan Meng, Sha Liao, Nini Yuan, Zhen Liu, Chao Li, Zhiyong Liu, Lei Han, Zhiming Shen, Ao Chen, Yidi Sun, Yuliang Dong, Longqi Liu, Chengyu Li, Wu Wei
Published in
Nature methods. Jul 24, 2026. Epub Jul 24, 2026.
Abstract
The primate brain exhibits complex RNA alternative splicing heterogeneity crucial for functional complexity, yet systematic spatial isoform characterization has been lacking. We developed Fullscope-seq, a full-length single-molecule large field-of-view spatial transcriptomics sequencing method at single-cell resolution, based on programmed concatenation cDNA for multiple long-read sequencing platforms. Applying Fullscope-seq to the macaque brain, we uncovered thousands of genes exhibiting differential transcript usage (DTU) across cortical layers, cell types and brain regions. Fullscope-seq resolved hundreds of major isoform switches across distinct brain regions and identified DTUs between superficial and deep cortical layers. Cortical layer-specific DTUs showed cell-composition dependence, whereas regional DTUs were regulated according to both cellular composition and spatial contexts. These isoform variations showed substantial enrichment for neuropsychiatric disorder-associated genes and were conserved across platforms and species. Our study establishes a scalable framework for spatial isoform analysis and provides a resource for understanding transcriptomic diversity in complex tissues.
PMID:
42498883
Bibliographic data and abstract were imported from PubMed on 25 Jul 2026.
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