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Abstract: SA-PO994

Studying Organoid Phenotypes in CoQ10-Deficient Glomerulopathy

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology


  • Yu, Seyoung, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)
  • Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States
  • Gee, Heon Yung, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of)

Monogenic causes of steroid resistant nephrotic syndrome (SRNS) account for 11-30% of childhood. Genes involved in coenzyme Q10 (CoQ10) biosynthesis, such as PDSS2, COQ2, COQ6 and ADCK4, are well established causes of SRNS and focal segmental glomerulosclerosis (FSGS). CoQ10 is a component of the mitochondrial inner membrane which plays an important role in supporting electron transport of oxidative phosphorylation and protection from oxidative stress. ADCK4-deficient glomerulopathy can be partially treated by CoQ10 supplementation, but the therapeutic efficacy of this treatment is variable and has limitations. We here established a robust in vitro model system of CoQ10-deficient glomerulopathies to study the therapeutic effects of drugs using elaborate manipulations, and to better understand the disease and thereby develop more effective treatment.


We generated CoQ10-deficient kidney organoids from human induced pluripotent stem cells (iPSCs) using the well-established in vitro induction protocol (Taguchi et al). To establish CoQ10-deficient human iPSCs, gRNAs targeting PDSS2, COQ2, COQ6 or ADCK4 were used with Cas9 protein individually. We performed immunostaining and light microscopy analysis to evaluate the extent of their differentiation and further test the mitochondrial dysfunction to observe the phenotypic characteristics due to CoQ10 deficiency.


Gene ablation of the four genes in iPSCs was confirmed by sanger sequencing. CoQ10-deficiency did not lead to failure of induction to nephron progenitors in organoids. CoQ10-deficient kidney organoids were positive for NPHS1 (a podocyte marker), LTL (a proximal tubule marker), and ECAD (a distal tubule marker) expression, and no difference was observed when compared with control organoids. Further studies will assess mitochondrial dysfunction and ROS levels to quantify pathogenic characteristics


In conclusion, we have developed a modeling system of CoQ10-deficient glomerulopathy that can be used to further evaluate the efficacy of potential drugs for this disease.


  • Government Support – Non-U.S.