Autism is a highly heritable neurodevelopmental condition that is understood as a diverse spectrum of characteristics. In over 10% of autistic people, rare and de novo loss-of-functions mutations strongly predispose to profound autism and co-occurring developmental disorders and intellectual disabilities. Understanding how variants converge on specific brain circuits and cell populations during human brain development, particularly in less explored brain areas, will be crucial to understand the etiology of profound autism.

Supported by the Simons Foundation Autism Research Initiative, we charted the spatiotemporal expression patterns of 250 such autism susceptibility genes with characterized mutations, across the second trimester developing human forebrain. Profiling over 10 million cells, we found convergence of these genes across a small number of brain regional programs. The resulting STAGE atlas uniquely combines:

1. Single-cell resolution spatial gene expression of >10 million cells across diverse human brain regions at 3 timepoints in the second trimester.
2. Expert-annotated neuroanatomy and cell states to contextualize where genes are expressed.
3. State-of-the-art computational analyses to uncover co-expressing gene programs.

The initial spatial transcriptomics dataset can be interactively navigated and downloaded on this portal.

Publications

Datasets

Spatial data on Webatlas

10.8 million single cell and spatially resolved transcriptomes. The resulting data shows gene expression, brain regional annotation, and mapped cell types for each spatial tissue location.

Explore data

Our Team

Omer
Bayraktar

Principal Investigator

Wellcome Sanger Institute

Alexander
Aivazidis

Omics Computational Analysis

Wellcome Sanger Institute

Fani
Memi

Spatial Transcriptomics Specialist

Wellcome Sanger Institute

Koen
Rademaker

Omics Computational Analysis

Wellcome Sanger Institute

Mahmoud
Koko

Genetic Analysis

Wellcome Sanger Institute

Kenny
Roberts

Spatial Transcriptomics Data Generation

Wellcome Sanger Institute

Andrew
Trinh

Spatial Transcriptomics Data Generation

Wellcome Sanger Institute

Robert
Petryszak

Data Visualization Portal

Wellcome Sanger Institute

Vitalii
Kleshchevnikov

Omics Computational Analysis

Wellcome Sanger Institute

Elizabeth
Tuck

Histology specialist

Wellcome Sanger Institute

Steven
Lisgo

Tissue Sampling

Human Developmental Biology Resource

Tong
Li

Imaging Analysis

Wellcome Sanger Institute

Stanislaw
Makarchuk

Imaging Analysis

Wellcome Sanger Institute

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Tomasz
Nowakowski

Co-Principal Investigator

University of California, San Francisco

Hilary
Martin

Co-Principal Investigator

Wellcome Sanger Institute

Acknowledgements

Wellcome Sanger Institute; Human Developmental Biology Resource; Newcastle University; University of California, San Francisco; Simons Foundation Autism Research Initiative (SFARI); Patients.

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