Related Experiment Video
Updated: Aug 6, 2026
09:06
Spatially Resolved, Integrated Single-Cell Multiomic Profiling of the Transcriptome and Epigenomic Targets in Frozen Tissue Sections
Published on: June 12, 2026
Full-length single-cell spatial transcriptomics reveals spatial and cell-type-specific transcript isoforms in the
Hengxin Liu1, Yanhong Hong1,2, Yao Santo Zhang1,3
1Lingang Laboratory, Shanghai, China.
Nature Methods
|July 24, 2026
Summary
Scientists developed Fullscope-seq, a novel spatial transcriptomics method, to map RNA splicing in the primate brain. This reveals crucial gene expression differences linked to brain function and neuropsychiatric disorders.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- Primate brain RNA alternative splicing is complex and vital for function.
- Systematic spatial characterization of RNA isoforms has been limited.
Purpose of the Study:
- To develop and apply a novel method for high-resolution spatial transcriptomics of RNA isoforms in the primate brain.
- To characterize differential transcript usage (DTU) across different brain structures and cell types.
Main Methods:
- Developed Fullscope-seq: a full-length, single-molecule, large field-of-view spatial transcriptomics sequencing method.
- Utilized programmed concatenation cDNA for compatibility with multiple long-read sequencing platforms.
- Applied Fullscope-seq to the macaque brain at single-cell resolution.
Main Results:
- Discovered thousands of genes with differential transcript usage (DTU) across cortical layers, cell types, and brain regions.
- Identified hundreds of major isoform switches and DTUs between superficial and deep cortical layers.
- Found that cortical layer-specific DTUs depend on cell composition, while regional DTUs are influenced by both cell composition and spatial context.
Conclusions:
- Fullscope-seq provides a scalable framework for spatial isoform analysis in complex tissues.
- Identified isoform variations enriched for neuropsychiatric disorder-associated genes, conserved across species and platforms.
- Established a valuable resource for understanding transcriptomic diversity and its role in brain function and disease.
Related Concept Videos
01:30General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
01:32Chromatin Modification in iPS Cells
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...