Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential (original) (raw)

  1. Gabriel Walton1,2,
  2. Reina Aoki1,2,
  3. Karrie Brondell1,2,
  4. Jonathan Schug1,2,
  5. Alan Fox1,2,
  6. Olga Smirnova1,2,
  7. Craig Dorrell3,
  8. Laura Erker3,
  9. Andrew S. Chu4,
  10. Rebecca G. Wells5,
  11. Markus Grompe3,
  12. Linda E. Greenbaum6,7 and
  13. Klaus H. Kaestner1,2,8
  14. 1Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
  15. 2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
  16. 3Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97239, USA;
  17. 4Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA;
  18. 5Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
  19. 6Departments of Cancer Biology, Thomas Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA;
  20. 7Medicine, Thomas Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA

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.

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