Hepatocyte GSD1a

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USA 617-674-3260

DefiniGEN provide disease modelled glycogen storage disease type 1a hepatocytes which are highly functional patient-derived human hepatocytes. This genetic disease results from a deficiency in the glucose-6-phosphatase (G6P) enzyme which impairs the ability of the liver to produce free glucose from glycogen and from gluconeogenesis. The cells are generated using the dermal fibroblasts from a glycogen storage disease patient with mutations at the G6P gene positions G222R and Q3477. These cells can offer disease modelling and drug discovery researchers unprecedented tool for elucidating the underlying mechanisms of this and similar lysosomal storage diseases.



Figure 1. For production of DefiniGEN GSD1a cells, GSD1a patient fibroblasts are first reprogrammed into iPSC using Nobel prize winning technology developed by Yamanaka and colleagues. These iPSC are then differentiated into liver hepatocytes using the OptiDIFF protocol developed at the University of Cambridge-Laboratory for Regenerative Medicine.

  • Highly standardized cell product containing >98% human hepatocyte cells with consistent performance and biologically relevant data
  • Disease circuit verified two heterozygous mutations G222R and Q3477
  • Phenotypic analysis of the cells using periodic acid/diastase staining has demonstrated that the cells hyper accumulate glycogen as the glucose-6-phosphatase enzyme is not functional.

Disease circuit verification

Figure 2. DNA sequencing chromatogram illustrating the two heterozygous mutations found in Def-HEP GSD1a.

Detection of Glycogen Storage via PAS staining

Period acid-Schiff (PAS) staining revealed Def-HEP GSD1a hepatocytes accumulated substantially greater amounts of intracellular glycogen compared with iPSC derived hepatocytes from control subjects n=3 (figure 3a); BODIPY staining showed excessive production of intracellular lipid in Def-HEP GSD1a hepatocytes (figure 3b); and Def-HEP GSD1a hepatocytes secrete more lactate compared with iPSC derived hepatocytes from control subjects, as assessed by ELISA analysis of a 24-hour collection of cell culture medium. Error bars denote SEM. N=3 (Figure 3C).

Figure 3. a) Period acid-Schiff (PAS) staining revealed Def-HEP GSD1a hepatocytes accumulated substantially greater amounts of intracellular glycogen than did those of controls (figure 3a) and showed excessive production of lipid (figure 3b) and lactic acid (figure 3c) confirming the cellular disease phenotype. (Courtesy; Rashid et. al 2010).



Figure 4. PAS/Diastase staining of cryopreserved Def-HEP GSD1a. Magnification level: x400. (A) PAS/Diastase staining showing breakdown of accumulated glycogen in the cells. (B) PAS staining showing accumulation of glycogen in the cells.

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