A healthy human liver cell atlas reveals hepatic stellate cell heterogeneity

We generated a high-resolution cellular atlas of the healthy human liver by profiling the transcriptome of more than 25,000 individual liver cells using droplet-based RNA-sequencing. Recently published datasets and in situ hybridization were integrated to confirm, validate and locate newly identified cell populations. We identified, annotated and characterized a total of 23 cell subpopulations that represent the degree of heterogeneity of parenchymal (i.e. hepatocytes and cholangiocytes) and non-parenchymal liver cells (i.e. endothelial cells, stellate cells, macrophages and lymphoid cells). We successfully classified human hepatocytes and liver sinusoidal endothelial cells along the porto-central axis and for the first time reveal the existence of functionally specialized pericentral GPC3+ and periportal HHIP+ DBH+ hepatic stellate cells in the healthy human liver. Our study provides a description of the different cell compartments that enter into the composition of a healthy human liver and currently constitutes the biggest single-cell RNA sequencing dataset available on human healthy hepatocytes and hepatic stellate cells. We identified subsets of hepatic stellate cells characterized by distinct localization and physiological functions. Overall design: Single-cell RNA sequencing for two livers. First liver is represented by 2 samples for the parenchymal fraction and 2 samples for the non-parenchymal fraction. Second liver is represented by 1 sample for the parenchymal fraction, 2 samples for the non-parenchymal fraction and 1 sample for the whole fraction.