Hedgehog signaling maintains resident hepatic progenitors throughout life

Jason K. Sicklick, Yin Xiong Li, Alaa Melhem, Eva Schmelzer, Marzena Zdanowicz, Jiawen Huang, Montserrat Caballero, Jeff H. Fair, John W. Ludlow, Randall E. McClelland, Lola M. Reid, Anna Mae Diehl

Research output: Contribution to journalArticlepeer-review

159 Scopus citations

Abstract

Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for endodermal commitment and hepatogenesis, the possibility that it regulates liver turnover in adults had not been considered because mature liver epithelial cells lack Hedgehog signaling. Herein, we show that this pathway is essential throughout life for maintaining hepatic progenitors. Patched-expressing cells have been identified among endodermally lineage-restricted, murine embryonic stem cells as well as in livers of fetal and adult Ptc-lacZ mice. An adult-derived, murine hepatic progenitor cell line expresses Patched, and Hedgehog-responsive cells exist in stem cell compartments of fetal and adult human livers. In both species, manipulation of Hedgehog activity influences hepatic progenitor cell survival. Therefore, Hedgehog signaling is conserved in hepatic progenitors from fetal development through adulthood and may be a new therapeutic target in patients with liver damage.

Original languageEnglish (US)
Pages (from-to)G859-G870
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume290
Issue number5
DOIs
StatePublished - May 2006

Keywords

  • Indian hedgehog
  • Liver
  • Patched
  • Progenitor cell
  • Sonic hedgehog

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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