Skip to main content

Table 1 Summary of data supporting the contribution of different cell types to the origin of liver cancer

From: Current view of liver cancer cell-of-origin and proposed mechanisms precluding its proper determination

Liver tumor type

Purported CoO

Mouse model

Approach

References

HCC

Hepatocyte

Sox9-CreERT; R26RYFP; MUPuPA/HFD; STZ/HFD

DEN; GEMM;

lineage tracing

[35]

Opn-CreERT2; K19-CreERT2;

R26RYFP; AAV8-Tbg-Cre;

Rosa26loxP-mTom-stop-loxP–mGFP

Rosa26loxP-stop-loxP–ZsGreen1

Mdr2KO; Ptenflx/flx

DEN/CCl2; CDE or DDC diet; GEMM;

lineage tracing

[38]

hURI-tetOFFhep; (SA)CreERT2

R26RYFP; AAV8-Tbg-Cre;

Rosa26loxP-mTom-stop-loxP–mGFP

Sox9-CreERT; K19-CreERT2 R26RZsGreen

DEN/CCl2; GEMM;

lineage tracing

[41]

Hnf1b-CreER; R26RTom; Mdr2KO

DEN; GEMM;

lineage tracing

[44]

AAV8-Tbg-Cre; Foxl1-Cre; R26RYFP

DEN/CCl2; TCPOBOP GEMM;

lineage tracing

[45]

HCC; iCCA

CMV-SB; TREt-Yap-IRES-GFP;

EF1a-miR-30; EF1a-rtTA3-shp53; Cre-ER; trp53flx/flx;

EF1a-rtTA3-shAPC;

EF1a-NICD-IRES-mCherry

DEN; GEMM; HTVI;

lineage tracing

[51]

iCCA

CMV-SB; EF1a-HAmyrAKT1;

EF1a-MycNICD; AAV8-Tbg-Cre; R26RYFP

GEMM; HTVI; lineage tracing

[53]

Alb-CreERT2; K19-CreERT2; R26RNotch; R26RYFP; R26RYFP; Hes flx/flx

TAA; GEMM; lineage tracing

[60]

HCC; iCCA

CMV-SB; pT3-EF1a-HAmyrAKT;

pT3-EF1a-YapS127A;

pT3-EF1α-dnRBPJ; AAV8-Tbg-Cre; R26RYFP; Notch1 flx/flx;

Notch2 flx/flx;

HTVI; GEMM; lineage tracing

[61]

iCCA

Cholangiocyte

CK19-CreERT2; R26RYFP; trp53flx/flx

TAA; GEMM; lineage tracing

[67]

HCC; iCCA

Cholangiocyte

or hepatocyte

Alb-CreERT2; Alb-Cre;

CK19-CreERT2;

Ptenflx/+; Ptenflx/flx;

LSL-KrasG12D;

Rosa26loxP-mTom-stop-loxP–mGFP

GEMM; lineage tracing

[68]

HCC; iCCA

Hepatic Progenitor Cell

Wild type C57BL/6; pGCDNsam-Bmi1-IRES-EGFP; pGCDNsam-β-catenin-IRES-EGFP; CSH1-shBmi1-EF-1α-EGFP

Isolation and in vitro transduction of H-CFU-Cs; subcutaneous and intra-splenic cell transplantations

[73]

Alb-Cre; Savflx/flx; Mst1flx/flx; Mst2flx/flx

GEMM

[78]

Hepatoma

Alb-Cre; WW45flx/flx;

GEMM

[79]

HCC

Alb-Cre; Mst1–/–; Mst2flx/flx

GEMM

[80]

HCC; iCCA

Sox2-Cre; CAGG-CreER; Mst1Δ/Δ; Mst2flx/Δ

GEMM

[81]

Alb-Cre; Mx1-Cre; Ad-Cre; Nf2flx/flx; B6;129Gt[ROSA]26Sortm1Sho/J;

GEMM; lineage tracing; partial hepatectomy; cell transplantation

[82]

iCCA

or

HCC

Alb-Cre; R26lox-stop-lox-NICD-ires-nls-EGFP

Retro-c-Myc/Akt

GEMM; cell transplantation

[85]

Alb-Cre; LSL-KrasG12D; Hnf4αflx/flx;

LSL-IDH2R172K;

GEMM; DEN

[87]

Hepatic Progenitor Cell; hepatoblast; or hepatocyte

NOD/SCID;

Hras Luciferase/EGFP;

SV40LT-mCherry; sh-c-Myc

Cell transplantation; lentiviral transduction

[91]

HCC; iCCA

Hepatocyte

Alb-Cre; p19Arf−/−;

Rosa26loxP-mTom-stop-loxP–mGFP;

Mlklflx/flx; TLR2−/−; TLR3−/−; TLR4−/−; TLR7−/−; TLR9−/−;

CMV-SB;

pCaMIA- c-Myc-IRES-myrAKT1; pCaMIA-c-Myc-IRES-NrasG12V;

pCaggs-Tbx3; pCaggs-Prdm5

HTVI; GEMM;

[63]

HCC

Hepatocyte/ Hepatic Progenitor Cell

Alb-Cre; Atg5flx/flx; Atg7flx/flx;

Pten flx/+;

Rosa26loxP-mTom-stop-loxP–mGFP;

GEMM

[92]

  1. CCl4 carbon tetrachloride, CMV cytomegalovirus, DEN Diethylnitrosamine, GEMM genetically-modified mouse models, H-CFU-Cs hepatic colony-forming units in culture, HFD high fat diet, HTVI hydrodynamic tail-vein injection, MUP-uPA major urinary protein- urokinase-type plasminogen activator, STZ streptozotocin, TAA thioacetamide, TCPOBOP 3,30,5,50-tetrachloro-1,4-bis(pyridyloxy)benzene, SB Sleeping Beauty