Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development

Mutations are acquired frequently, such that each cell’s genome inscribes its history of cell divisions. Common genomic alterations involve loss of heterozygosity events spanning multiple genes. This study leverages loss of heterozygosity events revealed through single-cell RNA sequencing of mouse brain tissue.

LOH events are revealed as tracts of monoallelically expressed, constitutionally heterozygous SNVs, enabling simultaneous inference of developmental lineage and cell type identification.

This retrospective analytical approach integrates into existing scRNA-seq pipelines and is applicable where genetic engineering is prohibited, such as humans, offering advantages over traditional experimental lineage tracing methods.