Single-Cell Analysis of the Gene Expression Effects of Developmental Lead (Pb) Exposure on the Mouse Hippocampus

• DOI: 10.1093/toxsci/kfaa069
• Publication Date: 2020-05-20T19:31:08Z
• Authors: Kelly M Bakulski; John F Dou; Robert C Thompson; Christopher Lee; Lauren Y Middleton; Bambarendage P U ...; Sean P Ferris; Tamara R Jones; Kari Neier; Xiang Zhou; Maureen A Sartor; Saher S Hammoud; Dana C Dolinoy; Justin A Colacino
• Keywords: Cell type

Lead (Pb) exposure is ubiquitous with permanent neurodevelopmental effects. The hippocampus brain region involved in learning and memory heterogeneous cellular composition. cell type-specific responses to Pb are unknown. objective of this study examine perinatal treatment effects on adult gene expression, at the level individual cells. In mice perinatally exposed control water or a human physiologically relevant (32 ppm maternal drinking water) Pb, 2 weeks prior mating through weaning, we tested for expression differences 5 months age. We sequenced RNA from 5258 hippocampal cells (1) test averaged across all cells, (2) compare cluster composition by treatment, (3) pathway within clusters. Gene patterns revealed 12 clusters, mapping major expected types (eg, microglia, astrocytes, neurons, oligodendrocytes). Perinatal was associated 12.4% more oligodendrocytes (p = 4.4 × 10-21) mice. Across marker genes. Within (q < 0.05) caused differential endothelial, microglial, pericyte, astrocyte upregulated protein folding pathways microglia 3.4 10-9) stress response 3.2 10-5). Bulk tissue analysis may be influenced changes type composition, obscuring vulnerable types. This serves as biological reference future single-cell toxicant studies, ultimately characterize molecular cognition behavior.