Somatic mosaicism in the mature brain reveals clonal cellular distributions during cortical development
Martin W Breuss,
Addison J. Lana,
Traci Fang Newmeyer,
Martina P. Pasillas,
Lucitia Van Der Kraan,
NIMH Brain Somatic Mosaicism Network,
Christopher K Glass,
Joseph G Gleeson
Posted 10 Aug 2020
bioRxiv DOI: 10.1101/2020.08.10.244814
Posted 10 Aug 2020
The structure of the human neocortex underlies species-specific features and is a reflection of intricate developmental programs. Here we analyzed neocortical cellular lineages through a comprehensive assessment of brain somatic mosaicism - which acts as a neutral recorder of lineage history. We employed deep whole genome and variant sequencing in a single postmortem neurotypical human brain across 25 anatomic regions and three distinct modalities: bulk geographies, sorted cell types, and single nuclei. We identified 259 mosaic variants, revealing remarkable differences in localization, clonal abundance, cell type specificity, and clade distribution. We identified a set of hierarchical cellular diffusion barriers, whereby the left-right axis separation of the neocortex occurs prior to anterior-posterior and dorsal-ventral axis separation. We also found that stochastic distribution is a driver of clonal dispersion, and that rules regarding cellular lineages and anatomical boundaries are often ignored. Our data provides a comprehensive analysis of brain somatic mosaicism across the human cerebral cortex, deconvolving clonal distributions and migration patterns in the human embryo. ### Competing Interest Statement The authors have declared no competing interest.
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