Organism-wide single-cell transcriptomics of long-lived C. elegans daf-2 mutants reveals tissue-specific reprogramming of gene expression networks

Abstract

A critical requirement for a systems-level understanding of complex biological processes such as aging is the ability to directly characterize interactions between cells and tissues within a multicellular organism. C. elegans nematodes harboring mutations in the insulin-like receptor daf-2 exhibit dramatically-increased lifespans. To identify tissue-specific biochemical mechanisms regulating aging plasticity, we single-cell sequenced 3-mRNA libraries generated from seven populations of whole day-one adult wild-type and daf-2-/- worms using the 10x ChromiumV1platform. The age-synchronized samples were bioinformatically merged into a single aligned dataset containing 40,000 age-synchronized wild-type and daf-2-/- cellular transcriptomes partitioned into 101 clusters, using unsupervised machine-learning algorithms to identify common cell types. Here we describe the basic features of the adult C. elegans single-cell transcriptome and summarize functional alterations observed in the gene expression profiles of long-lived daf-2-/- worms. Comprehensive methods and datasets are provided. This is the first study to directly quantify cell-specific differential gene expression between two age-synchronized, genetically-distinct populations of multicellular organisms. This novel approach answers fundamental questions regarding tissue-specific regulation of gene expression and helps to establish a foundation for a comprehensive C. elegans single-cell gene expression atlas.