Preparation of HLS9 and HLM

HLS9 and HLM were prepared from the 102 individual human liver samples using a method described in previous publications (Wang et al., 2016; Shi et al., 2018). Briefly, ∼200 mg of individual liver tissues was homogenized in 0.5 ml PBS in 1.5 ml microcentrifuge tubes on ice using an automatic pestle (VWR International LLC, Chicago). The homogenates were then centrifuged twice at 9000g for 20 minutes at 4°C to remove the fat-containing top layers. The supernatant was collected as HLS9 and transferred to a clean tube. To prepare HLM and HLS9 were further centrifuged at 300,000g for 20 minutes at 4°C using an Optima MAX ultracentrifuge with a MLA-80 rotor (Beckman Coulter, Indianapolis, IN) (Braner et al., 2018). The pellet (HLM) formed after the centrifugation was then resuspended in PBS and transferred to a clean tube for storage. Total protein concentrations of HLS9 and HLM samples were determined using a Pierce BCA protein assay kit. Pooled HLS9 and HLM samples were prepared by mixing protein content–normalized aliquots of the given sample type from all individuals. Samples were kept on ice or at 4°C during the entire preparation process, and the prepared HLS9 and HLM samples were stored at −80°C until use. The recovery factors for HLS9 (s9 protein per gram liver) and HLM (microsomal protein per gram liver) (Wilson et al., 2003) were determined to be 107.3 ± 28.1 and 18.8 ± 6.4 mg/g liver, respectively.