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Updated: Feb 10, 2026
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Single-cell Profiling of Developing and Mature Retinal Neurons
Published on: April 19, 2012
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A Single-Cell and Spatial 3D Multi-omic Atlas of Developing Human Basal Ganglia and Inhibitory Neurons.
Matthew G Heffel1,2, Heng Xu3,4, Oier Pastor-Alonso5
1Department of Human Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA.
Biorxiv : the Preprint Server for Biology
|February 9, 2026
Summary
This study reveals the 3D genome and epigenomic changes during human basal ganglia development. It identifies gene regulatory networks crucial for medium spiny neuron development and links them to neuropsychiatric disease risk.
Area of Science:
- Neuroscience
- Developmental Biology
- Genomics
Background:
- The human basal ganglia (BG) are critical for motor and cognitive functions, developing from transient embryonic structures called ganglionic eminences (GEs).
- Understanding the epigenomic and 3D genomic regulation of GE development and subsequent neuron maturation is essential for deciphering brain development and disease.
Purpose of the Study:
- To elucidate the epigenomic and 3D-genomic dynamics during the specification and maturation of GEs and GE-derived neurons in the human brain.
- To identify regulatory programs governing the development of specific basal ganglia cell types, such as medium spiny neurons (MSNs).
- To investigate the relationship between gene regulatory regions in MSNs and genetic risk for neuropsychiatric disorders.
Main Methods:
- Single-nucleus methyl-3C sequencing (snm3C-seq) for joint epigenomic and 3D-genomic analysis.
- Highly-multiplexed spatial transcriptomics to map gene expression in developing brain tissues.
- Chromatin and RNA single-molecule imaging for high-resolution analysis of regulatory elements.
Main Results:
- Demonstrated heterogeneous developmental trajectories across GE subregions (LGE and CGE) during gestation and infancy.
- Identified synchronized 3D epigenome maturation underlying the specification of MSN subtypes.
- Observed transient remodeling of 3D genome conformation during neuronal and oligodendrocyte progenitor differentiation in infant brains.
- Found enrichment of MSN-active regulatory loci in regions associated with neuropsychiatric disease risk.
Conclusions:
- The study delineates complex, lineage-specific 3D genomic dynamics in human ventral progenitors and basal ganglia populations during the perinatal period.
- Findings provide insights into the regulatory mechanisms of human basal ganglia development and offer potential links to neuropsychiatric disease etiology.
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