Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver

• DOI: 10.1101/gr.267013.120
• Publication Date: 2021-03-01T21:15:23Z
• Authors: Ullas V. Chembazhi; Sushant Bangru; Mikel Hernaez; Auinash Kalsotra
• Keywords: Liver Regeneration

The adult liver has an exceptional ability to regenerate, but how it maintains its specialized functions during regeneration is unclear. Here, we used partial hepatectomy (PHx) in tandem with single-cell transcriptomics track cellular transitions and heterogeneities of ∼22,000 cells through the initiation, progression, termination phases mouse regeneration. Our results uncovered that, following PHx, a subset hepatocytes transiently reactivates early-postnatal-like gene expression program proliferate, while distinct population metabolically hyperactive appears compensate for any temporary deficits function. Cumulative EdU labeling immunostaining metabolic, portal, central vein–specific markers revealed that hepatocyte proliferation after PHx initiates midlobular region before proceeding toward periportal pericentral areas. We further demonstrate portal vein proximal retain their active state preserve essential proliferate nearby. Through combined analysis regulatory networks cell–cell interaction maps, found regenerating redeploy key developmental regulons, which are guided by extensive ligand-receptor-mediated signaling events between nonparenchymal cells. Altogether, our study offers detailed blueprint intercellular crosstalk reprogramming balances metabolic proliferative requirements liver.