MERFISH and snRNAseq analysis of healthy and disease human liver

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of
cell types and their heterogeneity within the human liver, but the spatial
organization at single-cell resolution has not yet been described. Here we
apply multiplexed error robust fluorescent in situ hybridization (MERFISH)
to map the zonal distribution of hepatocytes, spatially resolve subsets of
macrophage and mesenchymal populations, and investigate the relationship
between hepatocyte ploidy and gene expression within the healthy human
liver. We next integrated spatial information from MERFISH with the more
complete transcriptome produced by single-nucleus RNA sequencing
(snRNA-seq), revealing zonally enriched receptor-ligand interactions.
Finally, MERFISH and snRNA-seq analysis of fibrotic liver samples
identified two hepatocyte populations that expanded with injury and do not
have clear zonal distributions. Together these spatial maps of the healthy
and fibrotic liver provide a deeper understanding of the cellular and
spatial remodeling that drives disease which, in turn, could provide new
avenues for intervention and further study.