 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 17, 2024 |
| Title |
A Mouse Model for Metabolic Dysfunction-associated Steatotic Liver Disease and Hepatocellular Carcinoma [RNA-seq] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The lack of an appropriate preclinical model of metabolic dysfunction-associated steatotic liver disease (MASLD) that recapitulates the whole disease spectrum impedes exploration of disease pathophysiology and the development of effective treatment strategies. Considering the fact that MASLD patients accompanying type 2 diabetes mellitus (T2DM) have high risk of developing metabolic dysfunction-associated steatohepatitis (MASH), advanced fibrosis, and HCC, we treated low-dose streptozotocin (STZ; 40 mg/kg) for 5 consecutive days and subsequently fed a high-fat diet (HFD) to male C57BL/6J mice at 7 weeks of age (STZ+HFD). STZ+HFD mice gradually developed fatty liver, MASH, hepatic fibrosis, and hepatocellular carcinoma (HCC) in the context of metabolic dysfunction. In particular, from 20 weeks of age, MASH was evident, and from 32 weeks of age, advanced fibrosis was developed. At 38 weeks, a proportion of STZ+HFD mice developed HCC, which was subsequently observed in all mice up to 68 weeks of age. Furthermore, the hepatic transcriptomic features of STZ+HFD mice closely reflected those of obese patients with T2DM, MASH and MASLD-related HCC. Notably, dietary changes and tirzepatide administration alleviated MASH, hepatic fibrosis, and hepatic tumorigenesis in STZ+HFD mice. In conclusion, a murine model recapitulating the main histopathologic, transcriptomic, and metabolic alterations observed in MASLD patients with metabolic dysfunction was successfully established.
|
| |
|
| Overall design |
To investigate transcriptomic alterations during MASLD progression, we profiled hepatic transcriptome of the model mouse at different ages with RNA-seq (7 weeks, healthy control; 8 weeks, acute STZ-treated state; 14-20 weeks, MASL to MASH transition; 32 weeks, MASH with fibrosis; 44 weeks, MASH with advanced fibrosis; 50-56 weeks, MASLD-related dysplastic nodules and HCC.
Then we compared hepatic transcriptome of mice with that of human NAFLD patients with different MASLD acitivty score and fibrosis stage using RNA-seq profiling.
We also performed RNA-seq profiling in hepatic tumors developed in model mice at 44-56 weeks.
In addition, we performed RNA-seq profiling in the four groups of C57BL/6J mice clasffied by STZ treatment and dietary method (STZ+HFD, STZ+standard chow diet(SCD), HFD only, SCD only) at 20 and 32 weeks of age to examine how STZ+HFD mice rapidly progress to NASH.
And we performed RNA-seq profiling in the model mice with dietary change to chow for 6 or 18 weeks with control unchanged group, and the model mice treated with tirzepatide or vehicle for 10 to 11 weeks at different ages (21-32 weeks, 28-38 weeks, and 41-52 weeks).
|
| |
|
| Contributor(s) |
Jeong B, Choi W, Choi W, Kim H, Park J |
| Citation(s) |
39090079 |
| |
| Submission date |
Oct 25, 2023 |
| Last update date |
Aug 21, 2024 |
| Contact name |
Byung-Kwan Jeong |
| E-mail(s) |
[email protected]
|
| Organization name |
Asan Medical Center
|
| Department |
Pathology
|
| Street address |
88, Olympic-ro 43-gil
|
| City |
Songpa-Gu |
| State/province |
Seoul |
| ZIP/Postal code |
05505 |
| Country |
South Korea |
| |
|
| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (148)
|
| GSM7865084 |
Healthy control,7w, biological replication 1 |
| GSM7865085 |
Healthy control,7w, biological replication 2 |
| GSM7865086 |
Healthy control,7w, biological replication 3 |
| GSM7865087 |
Healthy control,7w, biological replication 4 |
| GSM7865088 |
Healthy control,7w, biological replication 5 |
| GSM7865089 |
Acutre streptozotocin-treated state,8w, biological replication 1 |
| GSM7865090 |
Acutre streptozotocin-treated state,8w, biological replication 2 |
| GSM7865091 |
Acutre streptozotocin-treated state,8w, biological replication 3 |
| GSM7865092 |
STZ+HFD model, 14w, biological replication 1 |
| GSM7865093 |
STZ+HFD model, 14w, biological replication 2 |
| GSM7865094 |
STZ+HFD model, 14w, biological replication 3 |
| GSM7865095 |
STZ+HFD model, 14w, biological replication 4 |
| GSM7865096 |
STZ+HFD model, 14w, biological replication 5 |
| GSM7865097 |
STZ+HFD model, 20w, biological replication 1 |
| GSM7865098 |
STZ+HFD model, 20w, biological replication 2 |
| GSM7865099 |
STZ+HFD model, 20w, biological replication 3 |
| GSM7865100 |
STZ+HFD model, 20w, biological replication 4 |
| GSM7865101 |
STZ+HFD model, 20w, biological replication 5 |
| GSM7865102 |
STZ+HFD model, 32w, biological replication 1 |
| GSM7865103 |
STZ+HFD model, 32w, biological replication 2 |
| GSM7865104 |
STZ+HFD model, 32w, biological replication 3 |
| GSM7865105 |
STZ+HFD model, 32w, biological replication 4 |
| GSM7865106 |
STZ+HFD model, 32w, biological replication 5 |
| GSM7865107 |
STZ+HFD model, 44w, biological replication 1 |
| GSM7865108 |
STZ+HFD model, 44w, biological replication 2 |
| GSM7865109 |
STZ+HFD model, 44w, biological replication 3 |
| GSM7865110 |
STZ+HFD model, 44w, biological replication 4 |
| GSM7865111 |
STZ+HFD model, 44w, biological replication 5 |
| GSM7865112 |
STZ+HFD model, 50w, biological replication 1 |
| GSM7865113 |
STZ+HFD model, 50w, biological replication 2 |
| GSM7865114 |
STZ+HFD model, 50w, biological replication 3 |
| GSM7865115 |
STZ+HFD model, 50w, biological replication 4 |
| GSM7865116 |
STZ+HFD model, 56w, biological replication 1 |
| GSM7865117 |
STZ+HFD model, 56w, biological replication 2 |
| GSM7865118 |
STZ+HFD model, 56w, biological replication 3 |
| GSM7865119 |
STZ+HFD model, 56w, biological replication 4 |
| GSM7865120 |
STZ+HFD model, 56w, biological replication 5 |
| GSM7865121 |
STZ+HFD model, 56w, biological replication 6 |
| GSM7865122 |
STZ+HFD model, 44w, hepatic tumor ID 03 |
| GSM7865123 |
STZ+HFD model, 44w, hepatic tumor ID 04 |
| GSM7865124 |
STZ+HFD model, 44w, hepatic tumor ID 05 |
| GSM7865125 |
STZ+HFD model, 44w, hepatic tumor ID 06 |
| GSM7865126 |
STZ+HFD model, 50w, hepatic tumor ID 07 |
| GSM7865127 |
STZ+HFD model, 50w, hepatic tumor ID 09 |
| GSM7865128 |
STZ+HFD model, 50w, hepatic tumor ID 10 |
| GSM7865129 |
STZ+HFD model, 50w, hepatic tumor ID 11 |
| GSM7865130 |
STZ+HFD model, 56w, hepatic tumor ID 13 |
| GSM7865131 |
STZ+HFD model, 56w, hepatic tumor ID 14 |
| GSM7865132 |
STZ+HFD model, 56w, hepatic tumor ID 18 |
| GSM7865133 |
STZ+HFD model, 56w, hepatic tumor ID 22 |
| GSM7865134 |
STZ+HFD model, 56w, hepatic tumor ID 24 |
| GSM7865135 |
STZ+HFD model, 56w, hepatic tumor ID 25 |
| GSM7865136 |
Control SCD fed mice without STZ treatment, 20w, biological replication 1 |
| GSM7865137 |
Control SCD fed mice without STZ treatment, 20w, biological replication 2 |
| GSM7865138 |
Control SCD fed mice without STZ treatment, 20w, biological replication 3 |
| GSM7865139 |
Control SCD fed mice without STZ treatment, 20w, biological replication 4 |
| GSM7865140 |
STZ+ SCD mice, 20w, biological replication 1 |
| GSM7865141 |
STZ+ SCD mice, 20w, biological replication 2 |
| GSM7865142 |
STZ+ SCD mice, 20w, biological replication 3 |
| GSM7865143 |
HFD fed mice without STZ treatment, 20w, biological replication 1 |
| GSM7865144 |
HFD fed mice without STZ treatment, 20w, biological replication 2 |
| GSM7865145 |
HFD fed mice without STZ treatment, 20w, biological replication 3 |
| GSM7865146 |
HFD fed mice without STZ treatment, 20w, biological replication 4 |
| GSM7865147 |
HFD fed mice without STZ treatment, 20w, biological replication 5 |
| GSM7865148 |
STZ+HFD model, 26w, without dietary intervention, biological replication 1 |
| GSM7865149 |
STZ+HFD model, 26w, without dietary intervention, biological replication 2 |
| GSM7865150 |
STZ+HFD model, 26w, without dietary intervention, biological replication 3 |
| GSM7865151 |
STZ+HFD model, 26w, without dietary intervention, biological replication 4 |
| GSM7865152 |
STZ+HFD model, 26w, dietary change to SCD for 6 weeks, biological replication 1 |
| GSM7865153 |
STZ+HFD model, 26w, dietary change to SCD for 6 weeks, biological replication 2 |
| GSM7865154 |
STZ+HFD model, 26w, dietary change to SCD for 6 weeks, biological replication 3 |
| GSM7865155 |
STZ+HFD model, 26w, dietary change to SCD for 6 weeks, biological replication 4 |
| GSM7865156 |
STZ+HFD model, 50w, without dietary intervention, biological replication 1 |
| GSM7865157 |
STZ+HFD model, 50w, without dietary intervention, biological replication 2 |
| GSM7865158 |
STZ+HFD model, 50w, without dietary intervention, biological replication 3 |
| GSM7865159 |
STZ+HFD model, 50w, without dietary intervention, biological replication 4 |
| GSM7865160 |
STZ+HFD model, 50w, dietary change to SCD for 18 weeks, biological replication 1 |
| GSM7865161 |
STZ+HFD model, 50w, dietary change to SCD for 18 weeks, biological replication 2 |
| GSM7865162 |
STZ+HFD model, 50w, dietary change to SCD for 18 weeks, biological replication 3 |
| GSM7865163 |
STZ+HFD model, 50w, dietary change to SCD for 18 weeks, biological replication 4 |
| GSM7865164 |
STZ+HFD model, 32w, treated with control vehicle for 11 weeks, biological replication 1 |
| GSM7865165 |
STZ+HFD model, 32w, treated with control vehicle for 11 weeks, biological replication 2 |
| GSM7865166 |
STZ+HFD model, 32w, treated with control vehicle for 11 weeks, biological replication 3 |
| GSM7865167 |
STZ+HFD model, 32w, treated with control vehicle for 11 weeks, biological replication 4 |
| GSM7865168 |
STZ+HFD model, 32w, treated with control vehicle for 11 weeks, biological replication 5 |
| GSM7865169 |
STZ+HFD model, 32w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 1 |
| GSM7865170 |
STZ+HFD model, 32w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 2 |
| GSM7865171 |
STZ+HFD model, 32w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 3 |
| GSM7865172 |
STZ+HFD model, 32w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 4 |
| GSM7865173 |
STZ+HFD model, 32w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 5 |
| GSM7865174 |
STZ+HFD model, 38w, treated with control vehicle for 10 weeks, biological replication 1 |
| GSM7865175 |
STZ+HFD model, 38w, treated with control vehicle for 10 weeks, biological replication 2 |
| GSM7865176 |
STZ+HFD model, 38w, treated with control vehicle for 10 weeks, biological replication 3 |
| GSM7865177 |
STZ+HFD model, 38w, treated with control vehicle for 10 weeks, biological replication 4 |
| GSM7865178 |
STZ+HFD model, 38w, treated with tirzepatide (109.5 nmol/kg) for 10 weeks, biological replication 1 |
| GSM7865179 |
STZ+HFD model, 38w, treated with tirzepatide (109.5 nmol/kg) for 10 weeks, biological replication 2 |
| GSM7865180 |
STZ+HFD model, 38w, treated with tirzepatide (109.5 nmol/kg) for 10 weeks, biological replication 3 |
| GSM7865181 |
STZ+HFD model, 38w, treated with tirzepatide (109.5 nmol/kg) for 10 weeks, biological replication 4 |
| GSM7865182 |
STZ+HFD model, 52w, treated with control vehicle for 11 weeks, biological replication 1 |
| GSM7865183 |
STZ+HFD model, 52w, treated with control vehicle for 11 weeks, biological replication 2 |
| GSM7865184 |
STZ+HFD model, 52w, treated with control vehicle for 11 weeks, biological replication 3 |
| GSM7865185 |
STZ+HFD model, 52w, treated with control vehicle for 11 weeks, biological replication 4 |
| GSM7865186 |
STZ+HFD model, 52w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 1 |
| GSM7865187 |
STZ+HFD model, 52w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 2 |
| GSM7865188 |
STZ+HFD model, 52w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 3 |
| GSM7865189 |
STZ+HFD model, 52w, treated with tirzepatide (109.5 nmol/kg) for 11 weeks, biological replication 4 |
| GSM7865190 |
Healthy liver donor, biological replication 1 |
| GSM7865191 |
Healthy liver donor, biological replication 2 |
| GSM7865192 |
Healthy liver donor, biological replication 3 |
| GSM7865193 |
Healthy liver donor, biological replication 4 |
| GSM7865194 |
NAFLD patient, NAFLD activity score 2-3, fibrosis stage 1, biological replication 1 |
| GSM7865195 |
NAFLD patient, NAFLD activity score 2-3, fibrosis stage 1, biological replication 2 |
| GSM7865196 |
NAFLD patient, NAFLD activity score 2-3, fibrosis stage 1, biological replication 3 |
| GSM7865197 |
NAFLD patient, NAFLD activity score 2-3, fibrosis stage 1, biological replication 4 |
| GSM7865198 |
NAFLD patient, NAFLD activity score 2-3, fibrosis stage 1, biological replication 5 |
| GSM7865199 |
NAFLD patient, NAFLD activity score 2-3, fibrosis stage 1, biological replication 6 |
| GSM7865200 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 1, biological replication 1 |
| GSM7865201 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 1, biological replication 2 |
| GSM7865202 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 1, biological replication 3 |
| GSM7865203 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 1, biological replication 4 |
| GSM7865204 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 1, biological replication 5 |
| GSM7865205 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 2, biological replication 1 |
| GSM7865206 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 2, biological replication 2 |
| GSM7865207 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 2, biological replication 3 |
| GSM7865208 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 2, biological replication 4 |
| GSM7865209 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 2, biological replication 5 |
| GSM7865210 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 3, biological replication 1 |
| GSM7865211 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 3, biological replication 2 |
| GSM7865212 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 3, biological replication 3 |
| GSM7865213 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 3, biological replication 4 |
| GSM7865214 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 3, biological replication 5 |
| GSM7865215 |
NAFLD patient, NAFLD activity score 5-6, fibrosis stage 3, biological replication 6 |
| GSM7865216 |
NAFLD patient, NAFLD activity score 4-7, fibrosis stage 4, biological replication 1 |
| GSM7865217 |
NAFLD patient, NAFLD activity score 4-7, fibrosis stage 4, biological replication 2 |
| GSM7865218 |
NAFLD patient, NAFLD activity score 4-7, fibrosis stage 4, biological replication 3 |
| GSM7865219 |
NAFLD patient, NAFLD activity score 4-7, fibrosis stage 4, biological replication 4 |
| GSM7865220 |
NAFLD patient, NAFLD activity score 4-7, fibrosis stage 4, biological replication 5 |
| GSM7865221 |
NAFLD patient, NAFLD activity score 4-7, fibrosis stage 4, biological replication 6 |
| GSM8191460 |
HFD fed mice without STZ treatment, 32w, batch 9, biological replication 1 |
| GSM8191461 |
HFD fed mice without STZ treatment, 32w, batch 9, biological replication 2 |
| GSM8191462 |
HFD fed mice without STZ treatment, 32w, batch 9, biological replication 3 |
| GSM8191463 |
Control SCD fed mice without STZ treatment, 32w, batch 9, biological replication 1 |
| GSM8191464 |
Control SCD fed mice without STZ treatment, 32w, batch 9, biological replication 2 |
| GSM8191465 |
Control SCD fed mice without STZ treatment, 32w, batch 9, biological replication 3 |
| GSM8191466 |
Control SCD fed mice without STZ treatment, 32w, batch 9, biological replication 4 |
| GSM8191467 |
STZ+ SCD mice, 32w, batch 9, biological replication 1 |
| GSM8191468 |
STZ+ SCD mice, 32w, batch 9, biological replication 2 |
| GSM8191469 |
STZ+ SCD mice, 32w, batch 9, biological replication 3 |
|
| This SubSeries is part of SuperSeries: |
| GSE246223 |
A Mouse Model for Metabolic Dysfunction-associated Steatotic Liver Disease and Hepatocellular Carcinoma |
|
| Relations |
| BioProject |
PRJNA1032104 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE246221_rawcounts_allsamples_human.txt.gz |
2.4 Mb |
(ftp)(http) |
TXT |
| GSE246221_rawcounts_allsamples_mouse.txt.gz |
5.0 Mb |
(ftp)(http) |
TXT |
| GSE246221_rawcounts_newsamples_mouse.txt.gz |
793.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...