Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential

Genes Dev. 2011 Jun 1;25(11):1185-92. doi: 10.1101/gad.2027811.


Isolation of hepatic progenitor cells is a promising approach for cell replacement therapy of chronic liver disease. The winged helix transcription factor Foxl1 is a marker for progenitor cells and their descendants in the mouse liver in vivo. Here, we purify progenitor cells from Foxl1-Cre; RosaYFP mice and evaluate their proliferative and differentiation potential in vitro. Treatment of Foxl1-Cre; RosaYFP mice with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet led to an increase of the percentage of YFP-labeled Foxl1(+) cells. Clonogenic assays demonstrated that up to 3.6% of Foxl1(+) cells had proliferative potential. Foxl1(+) cells differentiated into cholangiocytes and hepatocytes in vitro, depending on the culture condition employed. Microarray analyses indicated that Foxl1(+) cells express stem cell markers such as Prom1 as well as differentiation markers such as Ck19 and Hnf4a. Thus, the Foxl1-Cre; RosaYFP model allows for easy isolation of adult hepatic progenitor cells that can be expanded and differentiated in culture.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation*
  • Cell Lineage
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Hepatocyte Nuclear Factor 3-alpha / genetics
  • Hepatocyte Nuclear Factor 3-alpha / metabolism*
  • Integrases / genetics
  • Integrases / metabolism
  • Liver / cytology*
  • Mice
  • SOX9 Transcription Factor / metabolism
  • Stem Cells / cytology*


  • Biomarkers
  • Foxa1 protein, mouse
  • Hepatocyte Nuclear Factor 3-alpha
  • SOX9 Transcription Factor
  • Sox9 protein, mouse
  • Cre recombinase
  • Integrases