Human Brain Barcodes

Abstract

AbstractDynamic CpG methylation “barcodes” were read from 15,000 to 21,000 single cells from three human male brains. To overcome sparse sequencing coverage, the barcode had ∼31,000 rapidly fluctuating X-chromosome CpG sites (fCpGs), with at least 500 covered sites per cell and at least 30 common sites between cell pairs (average of ∼48). Barcodes appear to start methylated and record mitotic ages because excitatory neurons and glial cells that emerge later in development were less methylated. Barcodes are different between most cells, with average pairwise differences (PWDs) of ∼0.5 between cells. About 10 cell pairs per million were more closely related with PWDs < 0.05. Barcodes appear to record ancestry and reconstruct trees where more related cells had similar phenotypes, albeit some pairs had phenotypic differences. Inhibitory and excitatory neurons both showed evidence of tangential migration with related cells in different cortical regions. fCpG barcodes become polymorphic during development and can distinguish between thousands of human cells.