Fig. 3

VEGFA mRNA-LNP induces BEC-to-hepatocyte conversion and promotes liver repair in chronic CDE/p21 and acute APAP/p21 liver injury models in Kdr-2A-CreERT2-2A-eYFP mice (A and B) Expression of KDR (red) in BECs (green) depicted by arrowheads 3 days after injury in female mice in CDE/p21 (A) and APAP/p21 (B) models. (C) Schematic depicting the CDE/p21 model. (D) Closeup images of a bile duct showing tdTomato+ EpCAM+ BECs in CDE/p21 injury model. (E) Stitched immunofluorescence images of tdTomato+ areas (outlined yellow) in CDE/p21 injury model. Quantification of the tdTomato+ areas in both groups. (F) Representative brightfield images of Oil Red O-stained liver showing lipids in CDE/p21 injury model. Quantification of the percentage of Oil Red O-stained areas averaged from three different fields in each mouse (n = 3 mice per group). (G) Immunofluorescence images of tdTomato+ hepatocytes co-stained with HNF4A or CD26 (outlined and identified with asterisk) in CDE/p21 injury model. (H) Schematic of the APAP/p21 injury model with 300 mg/kg for males (n = 6) or 500 mg/kg for females (n = 6). (I) Stitched immunofluorescence images of tdTomato+ areas (outlined yellow) and quantification of tdTomato+ areas in APAP/p21 injury model. (J) Immunofluorescence images of tdTomato+ hepatocytes (outlined and identified with asterisk) in APAP/p21 injury model co-stained with HNF4A (green) or CD26 (green). (K) Immunofluorescence images of YFP+ liver cells in Kdr-2A-CreERT2-2A-eYFP mice 3 days after APAP (400 mg/kg for male or 500 mg/kg for female). Closeups show BECs co-expressing YFP (green) and EpCAM (red) (arrowheads) and large intermediate hepatocyte-like cells expressing YFP (green) (arrows). Numerical data are presented as mean ± SD. Two-tailed Student?s t test, ?p < 0.05, ??p < 0.01, ???p < 0.001. See also Figure S4.