Diploid hepatocytes drive physiological liver renewal in adult humans

Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung

Beitragende

Abstract

Physiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon (14C) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age <3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show more than 7-fold higher annual birth rates than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between diploid and polyploid hepatocytes are limited under homeostatic conditions. With these findings, we present an integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.

Details

OriginalspracheEnglisch
Seiten (von - bis)499-507.e1-e12
Seitenumfang22
FachzeitschriftCell systems
Jahrgang13
Ausgabenummer6
PublikationsstatusVeröffentlicht - 15 Juni 2022
Peer-Review-StatusJa

Externe IDs

Scopus 85131786768
unpaywall 10.1016/j.cels.2022.05.001
WOS 000814124400006
ORCID /0000-0003-1065-4107/work/141543980
ORCID /0000-0001-6466-2589/work/142238092
ORCID /0000-0003-0137-5106/work/142244261

Schlagworte

Forschungsprofillinien der TU Dresden

  • Regenerative Therapien - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Neurowissenschaften - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Metabolische Erkrankungen - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes

DFG-Fachsystematik nach Fachkollegium

  • Molekulare Biologie und Physiologie von Nerven- und Gliazellen - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Entwicklungsneurobiologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Biomaterialien - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Entwicklungsbiologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Allgemeine Genetik und funktionelle Genomforschung - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Molekulare und zelluläre Neurologie und Neuropathologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Immunologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Zellbiologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes

Ziele für nachhaltige Entwicklung

  • SDG 3 – Gute Gesundheit und Wohlergehen - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes

ASJC Scopus Sachgebiete

  • Pathologie und Forensische Medizin - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Zellbiologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes
  • Histologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes

Schlagwörter

  • Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes

Bibliotheksschlagworte

  • 570 Biowissenschaften; Biologie - Adult, Child, Preschool, Diploidy, Hepatocytes, Humans, Liver/metabolism, Polyploidy, Retrospective Studies, Homeostasis, Aneuploidy, Proliferation, Birth, Cells, Dynamics, Polyploidization, Turnover, Age, Mature hepatocytes