GSE172231
Adult Phenotypes and Gene Expression in the Brain at Single Cell Resolution After Developmental Alcohol Exposure in Drosophila
Fetal alcohol exposure can lead to developmental abnormalities, intellectual disability, and behavioral changes, collectively termed fetal alcohol spectrum disorder (FASD). In 2015, the CDC found that 1 in 10 pregnant women report alcohol use and more than 3 million women in the USA are at risk of exposing their developing baby to alcohol. Identifying genetic risk alleles for FASD is challenging, since time, dose and frequency of exposure are often unknown, and phenotypic manifestations of FASD are diverse and become evident long after exposure. Drosophila melanogaster presents an excellent model to study developmental effects of alcohol exposure, because virtually unlimited numbers of individuals of the same genotype can be reared rapidly and economically under well-controlled environmental conditions without regulatory restrictions.  Furthermore, flies exposed to alcohol undergo physiological and behavioral changes that resemble human alcohol-related phenotypes. Flies reared on ethanol-supplemented medium show decreased viability, reduced sensitivity to ethanol, and disrupted sleep and activity patterns. To assess alcohol-modulated gene expression in the brains of flies reared on alcohol, we performed single cell RNA sequencing and resolved cell clusters with differentially expressed genes representing distinct neuronal and glial populations. We observed extensive sexual dimorphism. Two clusters associated with glial biomarkers showed greater differential gene expression in males, whereas mushroom body-derived cells exhibited a greater degree of differential gene expression in females.  Results obtained from these studies provide a blueprint for translational studies on alcohol-induced effects on gene expression in the brain that may contribute to or result from FASD in human populations. Overall design: single-cell RNA-seq profiling of 8 samples consisting of 20 Drosophila brains each, 2 conditions (reference and alcohol supplemented growth media), 2 sexes (male and female) and 2 replicates