Contributions of new hepatocyte lineages to liver growth, maintenance, and regeneration in mice.

Unlabelled: The contributions that de novo differentiation of new hepatocyte lineages makes to normal liver physiology are unknown. In this study, a system that uniquely marks cells during a finite period following primary activation of a serum albumin gene promoter/enhancer-driven Cre recombinase (albCre) transgene was used to investigate birthrates of new hepatocyte lineages from albumin (Alb)-naive precursors in mice. Elapsed time was measured with a two-color fluorescent marker gene that converts from expressing tandem dimer Tomato (tdT; a red fluorescent protein) to expressing green fluorescent protein (GFP) following primary exposure to Cre.

Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration.

Cells require ribonucleotide reductase (RNR) activity for DNA replication. In bacteria, electrons can flow from NADPH to RNR by either a thioredoxin-reductase- or a glutathione-reductase-dependent route. Yeast and plants artificially lacking thioredoxin reductases exhibit a slow-growth phenotype, suggesting glutathione-reductase-dependent routes are poor at supporting DNA replication in these organisms.