Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States; Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, The Hebrew University School of Medicine, Jerusalem, Israel
James Boocock
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
Longhua Guo
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
Stefan Zdraljevic
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, United States
Genetic regulation of gene expression underlies variation in disease risk and other complex traits. The effect of expression quantitative trait loci (eQTLs) varies across cell types; however, the complexity of mammalian tissues makes studying cell-type eQTLs highly challenging. We developed a novel approach in the model nematode Caenorhabditis elegans that uses single-cell RNA sequencing to map eQTLs at cellular resolution in a single one-pot experiment. We mapped eQTLs across cell types in an extremely large population of genetically distinct C. elegans individuals. We found cell-type-specific trans eQTL hotspots that affect the expression of core pathways in the relevant cell types. Finally, we found single-cell-specific eQTL effects in the nervous system, including an eQTL with opposite effects in two individual neurons. Our results show that eQTL effects can be specific down to the level of single cells.
