title: Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential.
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.
authors.affiliation: Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: Soona
authors.initials: S
authors.lastname: Shin
authors.forename: Gabriel
authors.initials: G
authors.lastname: Walton
authors.forename: Reina
authors.initials: R
authors.lastname: Aoki
authors.forename: Karrie
authors.initials: K
authors.lastname: Brondell
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schug
authors.forename: Alan
authors.initials: A
authors.lastname: Fox
authors.forename: Olga
authors.initials: O
authors.lastname: Smirnova
authors.forename: Craig
authors.initials: C
authors.lastname: Dorrell
authors.forename: Laura
authors.initials: L
authors.lastname: Erker
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Chu
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Wells
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
authors.forename: Linda E
authors.initials: LE
authors.lastname: Greenbaum
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D051379:Mice; D055758:SOX9 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D015415:Biomarkers; C496500:Foxa1 protein, mouse; D051541:Hepatocyte Nuclear Factor 3-alpha; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C045073:Cre recombinase; D019426:Integrases