Identification of cell type marker genes of the brain and their use in estimation of cell type proportions

Establishing the molecular diversity of cell types is crucial for the study of the nervous system. I compiled a cross-laboratory database of mouse brain cell type-specific transcriptomes from 36 major cell types from across the mammalian brain using rigorously curated published data from pooled cell type microarray and single-cell RNA-sequencing (RNA-seq) studies. I used these data to identify cell type-specific marker genes, discovering a substantial number of novel markers, many of which we validated using computational and experimental approaches. By examining datasets with known cell type proportion differences, I further demonstrate that summarized expression of marker gene sets (MGSs) in bulk tissue data can be used to estimate the relative cell type abundance across samples. Using this approach, I show that majority of genes previously reported as differentially expressed in Parkinson’s disease can be attributed to the reduction in dopaminergic cell number rather than regulatory events. To facilitate use of this expanding resource, I provide a user-friendly web interface at www.neuroexpresso.org.Science, Faculty ofGraduat