Characterization of NGLY1 patient-derived midbrain organoids
2023
National Institutes of Health (NIH), Bethesda, USA
NGLY1 deficiency is an extremely rare autosomal recessive inherited disease caused by mutations in the NGLY1 gene. Patients with pathogenic mutations in NGLY1 have complex clinical symptoms including global developmental delays, motor dysfunction, and liver dysfunction. To better understand the pathogenesis of the disease and the neurological symptoms of NGLY1 deficiency, the researchers generated and characterized midbrain organoids using iPSCs from two patients with different disease-causing mutations and CRISPR-generated NGLY1 knockout iPSCs. NGLY1-deficient midbrain organoids were shown to exhibit altered neuronal development compared with a wild-type (WT) organoid. Both neuronal (TUJ1) and astrocytic glial fiber protein markers were reduced in midbrain organoids derived from NGLY1 patients, as was the neurotransmitter GABA. Interestingly, staining of the dopaminergic neuronal marker tyrosine hydroxylase showed a significant reduction in patient-derived iPSC organoids. These results provide a relevant NGLY1 disease model to investigate disease mechanisms and evaluate therapeutics to treat NGLY1 deficiency.
Generation and characterization of NGLY1 patient-derived midbrain organoids
Atena Farkhondeh, Wei Zheng
Added on: 03-14-2023
[1] https://www.frontiersin.org/articles/10.3389/fcell.2023.1039182/full?emci=c8fa6362-e6bd-ed11-a8e0-00224832e811&emdi=dec475fa-b4be-ed11-a8e0-00224832e811&ceid=2015591
