mmpc-logo mmpc-logo
twitter-logo @NationalMMPC
| Create Account | login
Human iPSC-derived cerebral organoids model features of Leigh syndrome and
reveal abnormal corticogenesis.
Authors Romero-Morales AI, Robertson GL, Rastogi A, Rasmussen ML, Temuri H, McElroy GS,
Chakrabarty RP, Hsu L, Almonacid PM, Millis BA, Chandel NS, Cartailler JP, Gama
Submitted By Submitted Externally on 10/5/2022
Status Published
Journal Development (Cambridge, England)
Year 2022
Date Published 10/1/2022
Volume : Pages 149 : Not Specified
PubMed Reference 35792828
Abstract Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents
with bilateral brain lesions caused by defects in the mitochondrial respiratory
chain and associated nuclear-encoded proteins. We generated human induced
pluripotent stem cells (iPSCs) from three LS patient-derived fibroblast lines.
Using whole-exome and mitochondrial sequencing, we identified unreported
mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and
dihydrolipoyl dehydrogenase (GM01503, DLD). These LS patient-derived iPSC lines
were viable and capable of differentiating into progenitor populations, but we
identified several abnormalities in three-dimensional differentiation models of
brain development. LS patient-derived cerebral organoids showed defects in
neural epithelial bud generation, size and cortical architecture at 100 days.
The double mutant MT-ATP6/PDH line produced organoid neural precursor cells with
abnormal mitochondrial morphology, characterized by fragmentation and
disorganization, and showed an increased generation of astrocytes. These studies
aim to provide a comprehensive phenotypic characterization of available
patient-derived cell lines that can be used to study Leigh syndrome.


About MMPC
Animal Husbandry
Tests Data
Search Data
MMPC Centers


Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping

2017 National MMPC. All Rights Reserved.