Gwendolyn E. Kaeser

TL;DR: A scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex demonstrates a robust and scalable method for identifying and categorizing single nuclear transcriptomes.

TL;DR: Improved high-throughput methods for single-nucleus droplet-based sequencing and single-cell transposome hypersensitive site sequencing are reported, which revealed regulatory elements and transcription factors that underlie cell-type distinctions and mapped disease-associated risk variants to specific cellular populations, which provided insights into normal and pathogenic cellular processes in the human brain.

TL;DR: The authors developed pathway and gene set overdispersion analysis (PAGODA) to resolve multiple, potentially overlapping aspects of transcriptional heterogeneity by testing gene sets for coordinated variability among measured cells.

TL;DR: For example, this article described recombination of the Alzheimer's disease-related gene APP in human neurons, occurring mosaically as thousands of variant "genomic cDNAs" (gencDNAs).

TL;DR: These data identify somatic genomic changes in single neurons, affecting known and unknown loci, which are increased in sporadic AD, and further indicate functionality for genomic mosaicism in the CNS.