In search of a Drosophila core cellular network with single-cell transcriptome data

G3 (Bethesda). 2022 Aug 17;jkac212. doi: 10.1093/g3journal/jkac212. Online ahead of print.

Abstract

Along with specialized functions, cells of multicellular organisms also perform essential functions common to most if not all cells. Whether diverse cells do this by using the same set of genes, interacting in a fixed coordinated fashion to execute essential functions, or a subset of genes specific to certain cells, remains a central question in biology. Here, we focus on gene co-expression to search for a core cellular network across a whole organism. Single-cell RNA-sequencing (scRNA-seq) measures gene expression of individual cells, enabling researchers to discover gene expression patterns that contribute to the diversity of cell functions. Current efforts to study cellular functions focus primarily on identifying differentially expressed genes across cells. However, patterns of co-expression between genes are probably more indicative of biological processes than are the expression of individual genes. We constructed cell type-specific gene co-expression networks using single-cell transcriptome datasets covering diverse cell types from the fruit fly, Drosophila melanogaster. We detected a set of highly coordinated genes preserved across cell types and present this as the best estimate of a core cellular network. This core is very small compared with cell type-specific gene co-expression networks and shows dense connectivity. Gene members of this core tend to be ancient genes and are enriched for those encoding ribosomal proteins. Overall, we find evidence for a core cellular network in diverse cell types of the fruit fly. The topological, structural, functional and evolutionary properties of this core indicate that it accounts for only a minority of essential functions.

Keywords: Drosophila melanogaster; co-expression network; core cellular network; gene co-expression; phylostratigraphy; single-cell transcriptome; systems biology.