Single-nucleus resolution mapping of the adult C. elegans and its application to elucidate inter- and trans-generational response to alcohol
Lisa Truong,
Yen-Wei Chen,
Rio Barrere-Cain,
Max T. Levenson,
Karissa Shuck,
Wen Xiao,
Eduardo da Veiga Beltrame,
Blake Panter,
Ella Reich,
Paul W. Sternberg,
Xia Yang,
Patrick Allard
Affiliations
Lisa Truong
Human Genetics Graduate Program, UCLA, Los Angeles, CA 90095, USA
Yen-Wei Chen
Molecular Toxicology Inter-Departmental Program, UCLA, Los Angeles, CA 90095, USA
Rio Barrere-Cain
Institute for Society & Genetics, UCLA, Los Angeles, CA 90095, USA
Max T. Levenson
Molecular Toxicology Inter-Departmental Program, UCLA, Los Angeles, CA 90095, USA
Karissa Shuck
Institute for Society & Genetics, UCLA, Los Angeles, CA 90095, USA
Wen Xiao
Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA 90095, USA
Eduardo da Veiga Beltrame
Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Blake Panter
Institute for Society & Genetics, UCLA, Los Angeles, CA 90095, USA
Ella Reich
Institute for Society & Genetics, UCLA, Los Angeles, CA 90095, USA
Paul W. Sternberg
Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Xia Yang
Integrative Biology and Physiology Department, UCLA, Los Angeles, CA 90095, USA
Patrick Allard
Molecular Toxicology Inter-Departmental Program, UCLA, Los Angeles, CA 90095, USA; Institute for Society & Genetics, UCLA, Los Angeles, CA 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA 90095, USA; Corresponding author
Summary: Single-cell transcriptomic platforms provide an opportunity to map an organism’s response to environmental cues with high resolution. Here, we applied single-nucleus RNA sequencing (snRNA-seq) to establish the tissue and cell type-resolved transcriptome of the adult C. elegans and characterize the inter- and trans-generational transcriptional impact of ethanol. We profiled the transcriptome of 41,749 nuclei resolving into 31 clusters, representing a diverse array of adult cell types including syncytial tissues. Following exposure to human-relevant doses of alcohol, several germline, striated muscle, and neuronal clusters were identified as being the most transcriptionally impacted at the F1 and F3 generations. The effect on germline clusters was confirmed by phenotypic enrichment analysis as well as by functional validation, which revealed a remarkable inter- and trans-generational increase in germline apoptosis, aneuploidy, and embryonic lethality. Together, snRNA-seq represents a valuable approach for the detailed examination of an adult organism’s response to environmental exposures.
