Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations

TLDR

The liver, the largest solid organ, plays key metabolic and immune roles, yet its cellular composition and immune microenvironment remain poorly characterized. This study aims to map the cellular landscape of the human liver using single‑cell RNA sequencing. The authors profiled 8,444 parenchymal and non‑parenchymal cells from fresh tissue of five livers, integrating gene‑expression data, flow cytometry, and immunohistochemistry to delineate 20 distinct cell populations, including hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non‑conventional T cells, NK‑like cells, and distinct intrahepatic monocyte/macrophage subsets. Their analysis provides a comprehensive single‑cell atlas of the human liver, detailing resident cell characteristics and mapping the hepatic immune microenvironment.

Abstract

The liver is the largest solid organ in the body and is critical for metabolic and immune functions. However, little is known about the cells that make up the human liver and its immune microenvironment. Here we report a map of the cellular landscape of the human liver using single-cell RNA sequencing. We provide the transcriptional profiles of 8444 parenchymal and non-parenchymal cells obtained from the fractionation of fresh hepatic tissue from five human livers. Using gene expression patterns, flow cytometry, and immunohistochemical examinations, we identify 20 discrete cell populations of hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, conventional and non-conventional T cells, NK-like cells, and distinct intrahepatic monocyte/macrophage populations. Together, our study presents a comprehensive view of the human liver at single-cell resolution that outlines the characteristics of resident cells in the liver, and in particular provides a map of the human hepatic immune microenvironment.