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

S Shin, G Walton, R Aoki, K Brondell… - Genes & …, 2011 - genesdev.cshlp.org
S Shin, G Walton, R Aoki, K Brondell, J Schug, A Fox, O Smirnova, C Dorrell, L Erker…
Genes & development, 2011genesdev.cshlp.org
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 …
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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