Single-nucleus RNA sequencing reveals novel molecular signatures of healthy and chronically injured liver

Single‐cell transcriptome sequencing (scRNA‐seq) has recently revolutionized the understanding of mammalian liver biology and generated data at unprecedented detail. An obstacle in such studies, however, has been to generate highly viable single‐cell suspensions that represent a true snapshot of the intact liver tissue, without activation of de novo transcriptional stress responses. Past studies implemented diverse enrichment strategies to investigate rare and/or difficult‐to‐dissociate cell types; however, these approaches compromised normal cellular representation. Our aims were to: (a) develop an unbiased sampling approach to profile hepatic cells by single‐nucleus RNA sequencing (snRNA‐seq) of flash‐frozen tissue samples; (b) compare transcriptomics of healthy versus chronically injured liver; and (c) identify novel molecular signatures and potential diagnostic or prognostic biomarkers.