Parallel RNA and DNA analysis after deep sequencing (PRDD-seq) reveals cell type-specific lineage patterns in human brain

Stem cells and progenitors undergo a series of cell divisions to generate the neurons of the brain, and understanding this sequence is critical to studying the mechanisms that control cell division and migration in developing brain. Mutations that occur as cells divide are known as the basis of cancer but have more recently been shown to occur with normal cell divisions, creating a permanent, forensic map of the clonal patterns that define the brain. Here we develop technology to analyze both DNA mutations and RNA gene expression patterns in single cells from human postmortem brain, allowing us to define clonal patterns among different types of human brain neurons, gaining direct insight into how they form.