Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain.

Nature communications | 2021

Splicing varies across brain regions, but the single-cell resolution of regional variation is unclear. We present a single-cell investigation of differential isoform expression (DIE) between brain regions using single-cell long-read sequencing in mouse hippocampus and prefrontal cortex in 45 cell types at postnatal day 7 ( www.isoformAtlas.com ). Isoform tests for DIE show better performance than exon tests. We detect hundreds of DIE events traceable to cell types, often corresponding to functionally distinct protein isoforms. Mostly, one cell type is responsible for brain-region specific DIE. However, for fewer genes, multiple cell types influence DIE. Thus, regional identity can, although rarely, override cell-type specificity. Cell types indigenous to one anatomic structure display distinctive DIE, e.g. the choroid plexus epithelium manifests distinct transcription-start-site usage. Spatial transcriptomics and long-read sequencing yield a spatially resolved splicing map. Our methods quantify isoform expression with cell-type and spatial resolution and it contributes to further our understanding of how the brain integrates molecular and cellular complexity.

Pubmed ID: 33469025 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM135247
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH118934
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS105477
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIMH NIH HHS, United States
    Id: RF1 MH121267
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH125956
  • Agency: NIDA NIH HHS, United States
    Id: R01 DA003980
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: WT108749/Z/15/Z
  • Agency: NIDA NIH HHS, United States
    Id: T32 DA039080
  • Agency: NCI NIH HHS, United States
    Id: U24 CA180996
  • Agency: NHGRI NIH HHS, United States
    Id: U41 HG007234

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Oxford Nanopore Technologies (tool)

RRID:SCR_003756

Commercial organization developing a disruptive, proprietary technology platform for the direct, electronic analysis of single molecules. The instruments GridION and MinION are adaptable for the analysis of DNA, RNA, proteins, small molecules and other types of molecule. Consequently, the platform has a broad range of potential applications, including scientific research, personalized medicine, crop science and security / defence.

View all literature mentions

Systems Transcriptional Activity Reconstruction (tool)

RRID:SCR_005622

A next-generation web-based application that aims to provide an integrated solution for both visualization and analysis of deep-sequencing data, along with simple access to public datasets.

View all literature mentions

ENCODE (tool)

RRID:SCR_006793

Encyclopedia of DNA elements consisting of list of functional elements in human genome, including elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Enables scientific and medical communities to interpret role of human genome in biology and disease. Provides identification of common cell types to facilitate integrative analysis and new experimental technologies based on high-throughput sequencing. Genome Browser containing ENCODE and Epigenomics Roadmap data. Data are available for entire human genome.

View all literature mentions

Miltenyi Biotec (tool)

RRID:SCR_008984

An Organization portal, Antibody supplier, Service resource,

View all literature mentions

GENCODE (tool)

RRID:SCR_014966

Human and mouse genome annotation project which aims to identify all gene features in the human genome using computational analysis, manual annotation, and experimental validation.

View all literature mentions

Atac (tool)

RRID:SCR_015980

Alignment analysis software tool for comparative mapping between two genome assemblies or between two different genomes. It can cache intermediate results to speed a comparisons of multiple sequences.

View all literature mentions

Seurat (tool)

RRID:SCR_016341

Software as R package designed for QC, analysis, and exploration of single cell RNA-seq data. Enable users to identify and interpret sources of heterogeneity from single cell transcriptomic measurements, and to integrate diverse types of single cell data.

View all literature mentions

PromethION (tool)

RRID:SCR_017987

System offers real-time, long-read, direct DNA and RNA sequencing by Oxford Nanopore Technologies. System suitable for large scale projects such as population-scale sequencing or plant genomics, or for large scale service offerings. PromethION 24 and PromethION 48 systems offer ability to run 24 and 48 flow cells respectively. System allows on demand sequencing, using any flow cell at any time. Users can start and stop running individual experiments as required, or deploy multiple flow cells onto single experiments for greater speed or throughput.

View all literature mentions

C57BL/6NTac (tool)

RRID:MGI:2164831

laboratory mouse with name C57BL/6NTac from MGI.

View all literature mentions