Single-cell co-expression analysis reveals that transcriptional modules are shared across cell types in the brain.

Lien vers Pubmed [PMID] – 34015329

Lien DOI – S2405-4712(21)00153-810.1016/j.cels.2021.04.010

Cell Syst 2021 07; 12(7): 748-756.e3

Gene-gene relationships are commonly measured via the co-variation of gene expression across samples, also known as gene co-expression. Because shared expression patterns are thought to reflect shared function, co-expression networks describe functional relationships between genes, including co-regulation. However, the heterogeneity of cell types in bulk RNA-seq samples creates connections in co-expression networks that potentially obscure co-regulatory modules. The brain initiative cell census network (BICCN) single-cell RNA sequencing (scRNA-seq) datasets provide an unparalleled opportunity to understand how gene-gene relationships shape cell identity. Comparison of the BICCN data (500,000 cells/nuclei across 7 BICCN datasets) with that of bulk RNA-seq networks (2,000 mouse brain samples across 52 studies) reveals a consistent topology reflecting a shared co-regulatory signal. Differential signals between broad cell classes persist in driving variation at finer levels, indicating that convergent regulatory processes affect cell phenotype at multiple scales.