The truth lies somewhere in the middle: the cells responsible for liver tissue maintenance finally identified

• Published in: Cell regeneration Vol. 10; no. 1; pp. 1 - 28
• Main Author: Itoh, Tohru
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 04.08.2021; Springer Nature B.V; SpringerOpen
• Subjects: Animal husbandry; Biomedical and Life Sciences; Biomedicine; Carbohydrates; Cell Biology; Cell cycle; Cell differentiation; Cell division; Cell growth; Comment; CRISPR; Detoxification; Division of labor; Gene expression; Genetic analysis; Hepatocytes; Homeostasis; Immunoregulation; Insulin-like growth factor-binding protein 2; Life Sciences; Lipid metabolism; Liver; Macromolecules; Metabolism; Physiology; Protein biosynthesis; Regenerative medicine; Sequence analysis; Stem Cells; TOR protein; Veins & arteries; Zonation
• ISSN: 2045-9769; 2045-9769
• DOI: 10.1186/s13619-021-00090-8

Background The liver is a versatile organ with multiple physiological functions that are essential for vital activity of the organisms, ranging from metabolism of biological macromolecules including amino acids, lipids and carbohydrates, to serum protein synthesis, detoxification of xenobiotic compounds, production and secretion of bile, and immune regulation. (Itoh, 2016) Rather, a large number of studies in the last decade employing genetic lineage tracing analyses in mice based on the Cre/loxP-mediated heritable cell labeling and tracking system have convincingly demonstrated that hepatocyte renewal in mammalian livers is achieved by cell division of differentiated hepatocytes for physiological tissue turnover, and also for tissue regeneration in response to many if not all types of injury conditions. (Chen et al., 2020; Lin et al., 2018; Sun et al., 2020) A major cause of this conflicting and chaotic situation in this research field is that studies focusing on and tracing the fate of a specific subset of cells do not give information on the behavior of the other remaining cell populations, so that the presence of tissue-renewing activity in the former do not formally prove the absence of the same activity in the latter. [...]it should be necessary to perform side-by-side comparisons of hepatocyte subsets labeled by different Cre driver systems, as the hepatocyte behavior could be substantially influenced by experimental settings including institutional animal husbandry conditions. [...]the authors performed single-cell RNA sequencing analysis and CRISPR-mediated functional screening in vivo to characterize genes and pathways involved in hepatocyte proliferation, which implicated the IGFBP2-mTOR-CCND1 axis as a potentially important pathway responsible for proliferation of zone 2 hepatocytes.