![]() ![]() The introduction of clonal mosaicism in animal models has revealed lineage relationships across the mammalian body 7, 8. Mutations that occur in post-mitotic cells are ‘non-clonal’, whereas mutations in progenitors will transmit to daughters and are ‘clonal’ 6. It is estimated that at least one single nucleotide mutation accompanies each cell cycle during development 4, 5, and since cells can undergo hundreds of divisions, most cells in the body are genetically unique. Their genomes are marked by somatic mutations that accumulate during DNA replication, aging, and environmental exposures 1, 3. Our data provide a comprehensive analysis of brain somatic mosaicism across the neocortex and demonstrate cellular origins and progenitor distribution patterns within the human brain.įrom a single fertilized zygote, the human brain contains approximately 170 billion neurons and glial cells, part of the 30 trillion cells that make up the body. Clones across neocortically-derived cells were consistent with a dual origin from both dorsal and ventral cellular populations, similar to rodents, whereas the microglia lineage appeared distinct from other resident brain cells. ![]() We found that clones derived after the accumulation of 90–200 progenitors in the cerebral cortex tended to respect the midline axis, well before the anterior-posterior or ventral-dorsal axes, which represents a secondary hierarchy following the overall patterning of fore- and hindbrain domains. We identified 259 bona fide mosaic variants from the index case, then deconvolved distinct geographic, cell type, and clade organizations across the brain and other organs. We combined sampling of 25 distinct anatomic locations with deep whole genome sequencing in a neurotypical deceased individual and confirmed results with five samples collected from each of three additional donors. We analyzed neocortical clones in a postmortem human brain through a comprehensive assessment of brain somatic mosaicism, acting as neutral lineage recorders 1, 2. Here we sought to reconstruct processes that occur during early development through the sampling of adult human tissues. ![]() ![]() The structure of the human neocortex underlies species-specific traits and reflects intricate developmental programs. ![]()
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