title: Contributions of new hepatocyte lineages to liver growth, maintenance, and regeneration in mice.
abstract: 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. The accumulation of GFP and the decay of tdT each contributed to a regular fluorescence transition, which was calibrated in vivo. In normal adults, this system revealed that a steady-state level of 0.076% of all hepatocytes had differentiated within the previous 4 days from albCre-naive cell lineages. In comparison with resting adult livers, the relative abundance of these newborn hepatocytes was elevated 3.7-fold in the growing livers of juveniles and 8.6-fold during liver regeneration after partial hepatectomy in adults.
  
  
  CONCLUSIONS
  Newborn hepatocyte lineages arising from Alb-naive cells contribute to liver maintenance under normal conditions. Hepatocyte lineage birthrates can vary in response to the liver's physiological status.
authors.affiliation: Department of Immunology and Infectious Disease, Animal Resources Center, Montana State University, Bozeman, MT 59718, USA.
authors.forename: Sonya V
authors.initials: SV
authors.lastname: Iverson
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Comstock
authors.forename: Jean A
authors.initials: JA
authors.lastname: Kundert
authors.forename: Edward E
authors.initials: EE
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D002460:Cell Line; D022781:Hepatocytes; D008099:Liver / Q000254:growth & development*; D008115:Liver Regeneration; D051379:Mice