Fig. 3

Oval cells give rise to hepatocytes after AAF/PH injury but are not the primary contributor to hepatocyte regeneration. a Scheme illustrating DPPIV-chimeric lineage tracing system subjected to AAF/PH treatment. Representative histochemical and double-immunofluorescence images in serial liver sections at (b) 2 weeks and (c) 4 weeks after AAF/PH injury. b GGT(+)/DPPIV(−) foci are composed of hepatocytes [OV6(−)/HNF4α(+), CK19(−)/C/EBPα(+), CK19(−)/CPS1(+)] and differentiating oval cells [rectangle areas; OV6(+)/HNF4α(+), CK19(+)/C/EBPα(+), OV6(+)/Laminin(−)], which were in connection with the oval cell proliferation [OV6(+)/HNF4α(−), CK19(+)/C/EBPα(−)]. c Whole liver sections of DPPIV-chimeric livers from different rats at 4 weeks after AAF/PH injury demonstrate the contribution of oval cell–derived DPPIV(−) hepatocytes to liver regeneration after AAF/PH injury. d DPPIV-deficient rats received DPPIV(+) oval cells transplantation combined with AAF/PH injury. After 7 weeks following AAF/PH injury, DPPIV(+) oval cells regenerated DPPIV(+) hepatocyte clusters (arrows). At higher magnification, DPPIV(+) oval cell–derived hepatocytes were histologically identical to the surrounding DPPIV(−) hepatocytes. Dual immunofluorescence staining showed that DPPIV(+) oval cell–derived hepatocytes expressed DPPIV(+)/HNF4α(+) and DDPPIV(+)/C/EBPα(+). Original magnification: b 100×/zoom magnification 200×; c histochemical 100×/ double-immunofluorescence 40×; d histochemical 100×/zoom magnification 200×/ double-immunofluorescence 100×/zoom magnification 400×. Scale bars: b 100 μm; c 300 μm; d histochemical 300 μm/ double-immunofluorescence 100 μm