The mechanisms underlying
liver fibrosis are multifaceted and remain elusive with no approved antifibrotic treatments available. The adult zebrafish has been an underutilized tool to study
liver fibrosis. We aimed to characterize the single-cell transcriptome of the adult zebrafish liver to determine its utility as a model for studying
liver fibrosis. We used single-cell
RNA sequencing (
scRNA-seq) of adult zebrafish liver to study the molecular and cellular dynamics at a single-cell level. We performed a comparative analysis to
scRNA-seq of human liver with a focus on hepatic stellate cells (HSCs), the driver cells in
liver fibrosis.
scRNA-seq reveals transcriptionally unique populations of hepatic cell types that comprise the zebrafish liver. Joint clustering with human liver
scRNA-seq data demonstrates high conservation of transcriptional profiles and human marker genes in zebrafish. Human and zebrafish HSCs show conservation of transcriptional profiles, and we uncover
collectin subfamily member 11 (colec11) as a novel, conserved marker for zebrafish HSCs. To demonstrate the power of
scRNA-seq to study
liver fibrosis using zebrafish, we performed
scRNA-seq on our zebrafish model of a pediatric
liver disease with mutation in
mannose phosphate isomerase (MPI) and characteristic early
liver fibrosis. We found
fibrosis signaling pathways and upstream regulators conserved across MPI-depleted zebrafish and human HSCs. CellPhoneDB analysis of zebrafish transcriptome identified
neuropilin 1 as a potential driver of
liver fibrosis. Conclusion: This study establishes the first
scRNA-seq atlas of the adult zebrafish liver, highlights the high degree of similarity to human liver, and strengthens its value as a model to study
liver fibrosis.