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Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing
Published on: December 3, 2019
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Single-cell long-read sequencing-based mapping reveals specialized splicing patterns in developing and adult mouse
Anoushka Joglekar1,2,3, Wen Hu1,2, Bei Zhang4
1Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Nature Neuroscience
|April 9, 2024
Summary
Scientists mapped brain RNA isoforms, revealing significant cell-type and developmental variations. This brain isoform atlas highlights how RNA splicing impacts cell function and disease, with conserved and novel patterns across species.
Area of Science:
- Neuroscience
- Genomics
- Molecular Biology
Background:
- RNA isoforms are crucial for cell identity and function.
- A comprehensive map of brain RNA isoforms was previously unavailable.
- Understanding isoform diversity is key to deciphering brain complexity.
Purpose of the Study:
- To create a detailed atlas of full-length RNA isoforms in the brain.
- To investigate isoform variation across different brain regions, cell subtypes, developmental stages, and species.
- To explore the functional and disease implications of RNA isoform diversity.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) analysis.
- Comparative genomics across multiple species, including mice and humans.
- Analysis of splicing, transcription start sites, and polyadenylation sites.
Main Results:
- Full-length isoform expression varies for 72% of genes across multiple axes (development, region, cell type).
- Cell-type-specific splicing, transcription start, and polyadenylation sites significantly impact protein architecture and disease-associated variation.
- Developmental regulation of isoforms is more pronounced than regional regulation within the same cell type.
- Conserved isoform regulation exists between mouse and human brains, with additional cell-type specificity in humans.
Conclusions:
- The brain exhibits extensive, multi-axis RNA isoform variability, impacting cell identity and function.
- Isoform diversity plays a critical role in brain development, regional specialization, and disease susceptibility.
- This atlas provides a foundational resource for understanding brain complexity and developing targeted therapies.
