Fig. 1: Mapping hepatocytes within the architecture of the healthy human liver with MERFISH.

a Uniform manifold approximation and projection (UMAP) of all cells measured with MERFISH in the healthy human liver. b Heatmap displaying differentially expressed genes that identify each cluster. Normalized gene expression is indicated by color. Each column represents a single cell, and cells are grouped by cluster as indicated by color at the left of the heatmap. Genes are indicated on the top of the heatmap, and groups of genes characteristic of individual clusters are indicated on the bottom. Hierarchical clustering is shown at the right. Genes enriched in each cluster are shown. Genes may appear more than once if enriched in more than one cluster. c–e Distribution of cells expressing SDS and CYP2A6 (enriched in zone 1, c), ALDOB and ADH1B (most enriched in zone 2, d), and CYP2E1 and CYP1A2 (enriched in zone 3, e) in a section of liver tissue. Scale bars: 1000 μm. Expression level is measured in normalized gene expression. f Dot plot quantifying expression of genes mapped in c–e where the size of the dot represents the percentage of cells expressing a specific gene, and the color intensity indicates mean expression. g mRNA distributions across a single lobule. Each dot represents an individual mRNA transcript for the indicated gene oriented from a portal region at the top to a central region at the bottom. The relative abundance of each transcript across the lobule was then plotted (lower panel) for the same field of view. Scale bars: 50 μm. h Spatial distribution of cells assigned to each cluster of hepatocytes (Hep 1, Hep 2, or Hep 3). Hep 1 cells (purple) map to periportal areas (zone 1), Hep 3 cells (pink) map to pericentral areas (zone 3), and Hep 2 cells (brown) map between Hep 1 and Hep 3 cells (zone 2). Scale bar: 1000 μm.