Foxl1-Cre-marked adult hepatic progenitors have clonogenic and bilineage differentiation potential.
Genes Dev, 2011/6/01;25(11):1185-92.
Shin S[1], Walton G, Aoki R, Brondell K, Schug J, Fox A, Smirnova O, Dorrell C, Erker L, Chu AS, Wells RG, Grompe M, Greenbaum LE, Kaestner KH
Affiliations
PMID: 21632825DOI: 10.1101/gad.2027811
Impact factor: 12.89
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.
MeSH terms
Animals; Biomarkers; Cell Differentiation; Cell Lineage; Cell Proliferation; Cells, Cultured; Gene Expression Profiling; Gene Expression Regulation, Developmental; Hepatocyte Nuclear Factor 3-alpha; Integrases; Liver; Mice; SOX9 Transcription Factor; Stem Cells
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