Global analysis of transcriptome diversity at the single-cell level in human neurons
The diversity of neuronal cells in the human brain is thought to be reflected by the tremendous diversity of RNA molecules generated in each neuron by the process of alternative pre-mRNA splicing. But thus far, it is unknown if the diversity of splicing found in pooled neuronal tissues is indeed recapitulated within each individual neuron. Such molecular diversity underlies uniquely human responses in the brain and need to be quantified to identify key molecules that specify the identity of functioning neurons. To do so, we use an approach that integrates computational modeling and comprehensive single-cell measurements of the entire repertoire of RNA molecules in each individual neuron, for hundreds of neurons. We will utilize our methodology to measure if molecular diversity is affected when mutations associated with motor neuron disease are present in these cells.