Comprehensive whole-organism transcriptional mapping of transgenerational environmental response

Single-cell RNA transcriptomic technologies offer a unique opportunity to map an organism’s response to environmental cues with high resolution and identify sensitive cell types. Circumventing known limitations of single cell approaches, we developed a novel single-nucleus RNA-seq (snRNA-seq) approach in the adult nematode C. elegans. We previously used this approach to model Fetal Alcohol Syndrome Disorders and identify all the cell types in the adult progeny that are altered by parental ethanol exposure. Here, we will extend these studies to examine, for the first time, the entire repertoire of tissue- and cell-specific transcriptomes in the nematode and ask which cell types are the most affected by transgenerational (great-grand parental) ethanol exposure. To answer this question, we will expose C. elegans to several human-relevant doses of ethanol and combine snRNA-seq with computational analyses to identify differentially expressed genes and pathways at the cell type-specific level. We will complement this unprecedented transgenerational transcriptomic analysis with functional assays to validate the findings. Since an estimated 30% of women report drinking alcohol at any point during their pregnancy, it is vital to understand the long-term generational consequences of such exposure.