Liver Single-Cell Transcriptome Analysis of Cell-specific Dysregulation of Liver Cell Biology Following Intravenous Administration of AAV Vectors

Zhu et al. report the application of single-cell RNA-sequencing technology for profiling the cell-specific transgene expression and transcriptome dysregulation in mouse liver following intravenous administration of AAV vectors. By profiling 46,500 mouse liver cells, we have identified 3 separate clusters of hepatocytes (hep1, hep2 and hep3), endothelial cells, Kupffer cells and lymphocytes. Assessment of the AAVrh.10mCherry treated liver demonstrated transgene expression in not only hepatocytes, but in all cell types, with significant cell-type-specific expression heterogeneity. Large numbers of cell type-specific genes were up- and down-regulated in response to the AAV vectors. These observations provide insights into the liver cell-specific consequences of AAV-mediated liver gene transfer, far beyond the well-known organ-specific expression of the vector-delivered transgene. Overall design: Single-cell RNA-sequencing analysis of livers of wild-type, male, C57BL/6 mice following intravenous injection of PBS, AAVrh.10Null and AAVrh.10mCherry