Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential (original) (raw)
- Gabriel Walton1,2,
- Reina Aoki1,2,
- Karrie Brondell1,2,
- Jonathan Schug1,2,
- Alan Fox1,2,
- Olga Smirnova1,2,
- Craig Dorrell3,
- Laura Erker3,
- Andrew S. Chu4,
- Rebecca G. Wells5,
- Markus Grompe3,
- Linda E. Greenbaum6,7 and
- Klaus H. Kaestner1,2,8
- 1Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
- 2Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
- 3Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97239, USA;
- 4Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA;
- 5Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
- 6Departments of Cancer Biology, Thomas Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA;
- 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.
Footnotes
↵8 Corresponding author.
E-MAIL kaestner{at}mail.med.upenn.edu; FAX (215) 573-5892.Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.2027811.
Supplemental material is available for this article.
Received January 3, 2011.
Accepted March 31, 2011.
Copyright © 2011 by Cold Spring Harbor Laboratory Press