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A Single-Cell Transcriptomic Atlas of Human Neocortical Development during Mid-gestation
Damon Polioudakis1, Luis de la Torre-Ubieta2, Justin Langerman3
1Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
Neuron
|July 16, 2019
Summary
This study created a single-cell gene expression atlas of the developing human cortex, revealing new cell types and insights into neurogenesis and neuropsychiatric diseases like ASD and epilepsy.
Area of Science:
- Neuroscience
- Genomics
- Developmental Biology
Background:
- The developing human cortex is complex, with many cell types and regulatory networks yet to be fully understood.
- Previous studies often relied on bulk tissue analysis, limiting resolution.
- Understanding early cell fate decisions in human neurogenesis is crucial for comprehending brain development and disease.
Purpose of the Study:
- To create a high-resolution single-cell gene expression atlas of the developing human cortex.
- To characterize previously un Tknown cell types, including human subplate neurons.
- To investigate the relationship between cell-cycle progression, cell fate decisions, and gene expression during neurogenesis.
Main Methods:
- RNA sequencing of 40,000 individual cells from the developing human cortex.
- Comparative analysis of single-cell data with bulk tissue expression profiles.
- Systematic analysis of technical factors influencing gene expression data.
- Mapping of neuropsychiatric disease genes to specific cell types.
Main Results:
- Generated the first single-cell characterization of human subplate neurons and other novel cell types.
- Demonstrated that cell differentiation occurs on a transcriptomic continuum, with broad, mixed cell-type transcriptomes during differentiation.
- Identified specific cell types implicated in autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy through gene mapping.
- Developed CoDEx, an online portal for data access and browsing.
Conclusions:
- The single-cell atlas provides a foundational resource for understanding human neurogenesis, cortical evolution, and the cellular basis of neuropsychiatric disorders.
- Early cell fate decisions are linked to cell-cycle progression and occur along a continuum of gene expression.
- Specific cell types are implicated in the etiology of major neuropsychiatric diseases, opening avenues for targeted research and therapies.
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