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Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers MADM
Published on: May 8, 2020
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Cell-type-resolved somatic mosaicism reveals clonal dynamics of the human forebrain
Changuk Chung1,2, Xiaoxu Yang1,2,3, Robert F Hevner4,5
1Department of Neurosciences, University of California San Diego, La Jolla, CA, 92037, USA.
Biorxiv : the Preprint Server for Biology
|November 14, 2023
Summary
Investigating human brain development, this study uses cell-type-specific mosaic variant barcode analysis to reveal neuronal lineage relationships. Findings show restricted clonal spread in the hippocampus and neocortex, offering insights into forebrain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Understanding the human forebrain's cellular origins and lineage relationships is crucial but challenging.
- Direct observation in mature human brains is essential for clarifying structural organization and cell development.
Approach:
- Developed cell-type-specific Mosaic Variant Barcode Analysis (MVBA) using brain mosaic variation to study clonal dynamics.
- Analyzed mosaic variants (MVs) from four human brain hemispheres to deconvolve lineage relationships.
- Performed simultaneous genome-transcriptome analysis at single-cell and cell-type-specific levels.
Key Points:
- Local hippocampal excitatory neurons exhibit more restricted lineage compared to neocortical excitatory or basal ganglia inhibitory neurons.
- A subset of DLX1+ inhibitory neurons originates from the dorsal neocortex, sharing an origin with excitatory neurons.
- Clonal spread restrictions along the anterior-posterior axis precede those along the dorsal-ventral axis in the parietal lobe.
Conclusions:
- Cell-type-resolved somatic mosaicism is a powerful tool for uncovering human forebrain lineage relationships.
- This approach clarifies the developmental origins and spatial organization of diverse neuronal subtypes.
- The study provides critical insights into the cellular architecture and developmental processes of the human brain.
