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PMID: 21632825 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Genes & development ·Vol. 25 ·No. 11 ·2011-06-01 ·Pages 1185-92

Shin S, 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

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/metabolism Cell Differentiation Cell Lineage Cell Proliferation Cells, Cultured Gene Expression Profiling Gene Expression Regulation, Developmental Hepatocyte Nuclear Factor 3-alpha/genetics,metabolism Integrases/genetics,metabolism Liver/cytology Mice SOX9 Transcription Factor/metabolism Stem Cells/cytology
Chemicals
Biomarkers Foxa1 protein, mouse Hepatocyte Nuclear Factor 3-alpha SOX9 Transcription Factor Sox9 protein, mouse Cre recombinase Integrases
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Shin Soona
Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, USA.
Walton Gabriel
Aoki Reina
Brondell Karrie
Schug Jonathan
Fox Alan
Smirnova Olga
Dorrell Craig
Erker Laura
Chu Andrew S
Wells Rebecca G
Grompe Markus
Greenbaum Linda E
Kaestner Klaus H
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.2027811
Published
2011-06-01
Pages
1185-92
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC3110956
Subset
IM
Grants
NIDDK NIH HHS · P01 DK049210 · United States
NIDDK NIH HHS · P30 DK019525 · United States
Corrections
CommentIn
PMID: 22190378
External Links
PubMed source DOI: 10.1101/gad.2027811 PMC Full Text View journal details
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