Heterogeneity of monocyte-derived macrophages in NASH. In a mouse model of NAFLD, resident yolk sac-embryonic KCs are gradually lost, and this niche is subsequently repopulated by BM-derived monocytes. The resulting intrahepatic macrophage population is heterogeneous, consisting of many subsets including pre-monocyte-derived KCs and hepatic LAMs. Hepatic LAMs express osteopontin, are located in fibrotic zones, and possess a unique transcriptomic profile. What signals drive the differentiation of monocyte-derived KCs into hepatic LAMs is unclear. Whereas hepatic LAMs had a distinct ability to metabolize lipid compared to KCs, whether this has significance in their crosstalk with steatotic hepatocytes is also undefined.