Single-cell RNA sequencing reveals the heterogeneity of hepatic non-parenchymal cell responses to chronic PFO5DoDA exposure in male mice

Environ Pollut. 2024 Mar 8:123721. doi: 10.1016/j.envpol.2024.123721. Online ahead of print.ABSTRACTPerfluoroalkyl ether carboxylic acids (PFECA) have emerged as novel alternatives to legacy per- and polyfluoroalkyl substances (PFAS). Existing research has revealed hepatoxicity induced by various PFAS, including PFECA. However, these studies have primarily focused on overall changes in whole liver tissue, particularly in hepatocytes, with the impact of PFAS on diverse liver non-parenchymal cells (NPCs) still inadequately understood. In the present study, we examined the heterogeneous responses of hepatic NPCs following exposure to perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoDA), a type of PFECA, by administering PFO5DoDA (5 μg/L)-contaminated water to male mice for one year. Single-cell RNA sequencing (scRNA-seq) of 15 008 cells from the liver identified 10 distinct NPC populations. Notably, although relative liver weight remained largely unchanged following exposure to 5 μg/L PFO5DoDA, there was an observed increase in proliferating cells, indicating that proliferating NPCs may contribute to the hepatomegaly frequently noted in PFAS-exposed livers. There was also a considerable alteration in the composition of hepatic NPCs. Specifically, the total number of B cells decreased substantially, while many other cells, such as monocytes and macrophages, increased after PFO5DoDA exposure. In addition, interactions among the hepatic NPC populations changed variously after ...
Source: Environmental Pollution - Category: Environmental Health Authors: Source Type: research