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

Soona Shin, Gabriel Walton, Reina Aoki, Karrie Brondell, Jonathan Schug, Alan Fox, Olga Smirnova, Craig Dorrell, Laura Erker, Andrew S. Chu, Rebecca G. Wells, Markus Grompe, Linda E. Greenbaum, Klaus H. Kaestner

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1185-1192
Number of pages8
JournalGenes and Development
Volume25
Issue number11
DOIs
StatePublished - Jun 1 2011

Keywords

  • Bilineage
  • Foxl1
  • Liver
  • Progenitor cells
  • Sox9

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Shin, S., Walton, G., Aoki, R., Brondell, K., Schug, J., Fox, A., Smirnova, O., Dorrell, C., Erker, L., Chu, A. S., Wells, R. G., Grompe, M., Greenbaum, L. E., & Kaestner, K. H. (2011). Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential. Genes and Development, 25(11), 1185-1192. https://doi.org/10.1101/gad.2027811