Hepatocyte (NAFLD) TM6SF2 Liver Disease Model

NAFLD TM6SF2 disease modelled hepatocytes

DefiniGEN disease modelled NAFLD hepatocytes represent an optimized model for drug discovery applications and a principal tool for elucidating the underlying mechanisms of the disease.
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Product Overview

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat within the liver that can lead to inflammation, fibrosis, and hepatocellular carcinoma. There are a number of genetic factors which contribute to the occurrence of NAFLD, one of these is the transmembrane protein 6 superfamily member 2 (TM6SF2), in which loss of function has a significant associated risk for NAFLD. This validated disease model is one of a number of NAFLD genetic variants produced by DefiniGEN to support research and drug development in this important area.

Benefits
  • Disease circuit verified: Def-HEP NAFLD TM6SF2
  • Display multiple key hepatocyte markers A1AT, ALB, HNF4a
  • Phenotypic analysis verified fatty acid accumulation
  • Genetic manipulation does not negatively affect differentiation capacity into hepatocytes
Product Specification
Ordering information
Product ID Def-HEP NAFLD TM6SF2
Format Cryopreserved 
Cell number  4-6 million cells
Genetic background Non-alcoholic fatty liver disease 
Viability >70%
Pricing Request a quote
Technical Data
Disease circuit verification
Sanger sequencing of the edited TM6SF2 gene using CRISPR/Cas9 in the reference hiPSC line
Figure 1. Sanger sequencing of the edited TM6SF2 gene using CRISPR/Cas9 in the reference hiPSC line. (A) TM6SF2 gene in the wild-type line. (B) TM6S2 homozygous knock-in clone with E167K mutation (Glutamic acid to Lysine at position 167, exon 6).
Hepatocyte marker analysis
 Functional analysis of Def-HEP TM6SF2 cells.
Figure 2. Functional analysis of Def-HEP TM6SF2 cells. QPCR analysis indicates that the TM6SF2 CRISPR-modified cells can be successfully differentiated into hepatocyte cells that express key hepatocyte markers at similar levels to primary human hepatocytes (PHH).
NAFLD marker analysis
 Functional analysis of Def-HEP TM6SF2 cells.
Figure 3. Functional analysis of Def-HEP TM6SF2 cells. QPCR analysis indicates that the TM6SF2 CRISPR-modified hepatocytes express few key NAFLD markers at higher levels to Def-HEP Wild type cells.
Hepatocyte cell morphology
NAFLD TM6SF2 clone
Figure 4. Def-HEP NAFLD TM6SF2 cells exhibit typical hepatocyte cobblestone morphology.
Fatty acid accumulation
Fatty Acid Accumulation TM6SF2
Figure 5. Fatty acid accumulation in Def-HEP TM6SF2 cells. Both Oil Red O and BODIPY staining show a higher accumulation of lipids in Def-HEP TM6SF2 E167K when cultured in low-lipid media.