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Updated: Sep 30, 2025
Generation of Human Brain Organoids for Mitochondrial Disease Modeling
Published on: June 21, 2021
Abnormal mitochondria in Down syndrome iPSC-derived GABAergic interneurons and organoids
Lei Xu1, Hai-Qin Huo2, Kai-Qin Lu2
1School of Pharmacy, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China; State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Abstract:
Down syndrome (DS) is caused by trisomy 21, and it is characterized by developmental brain disorders and neurological dysfunction. Clinical studies and basic research have revealed that defects in mitochondrial function contribute to the pathogenesis of DS. However, the underlying mechanisms of mitochondrial dysfunction in DS remain unclear. In this study, we first generated GABAergic interneurons and medial ganglionic eminence (MGE) organoids from DS patients and control induced pluripotent stem cells. The mitochondria were abnormally clustered in the perinuclear region of GABA neurons and cell in MGE organoids from DS patients, which exhibited impaired mitochondrial function as assessed by seahorse oxidative phosphorylation assay. Inhibition of the DSCAM-PAK1 pathway by gene editing or treatment with a small molecule corrected mitochondrial perinuclear aggregation in cells from DS patients. Therefore, our study provides insight into the potential mechanism of mitochondrial dysfunction in DS.
