| RRC ID |
86226
|
| Author |
Kawano S, Saegusa C, Masano Y, Becker F, Nakamura M, Shiozawa S, Fujikura J, Toyohara T, Abe T, Okano H, Fujioka M.
|
| Title |
Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes.
|
| Journal |
J Vis Exp
|
| Abstract |
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) are mitochondrial disorders most commonly caused by a m.3243A>G variant in mitochondrial tRNALeu. To investigate the pathophysiology of MELAS, we generated brain organoids from multiple induced pluripotent stem cell (iPSC) lines derived from a patient with MELAS carrying the m.3243A>G variant. These lines share an identical nuclear genetic background but differ in their heteroplasmy levels involving the m.3243A>G variant. We observed significant differences in organoid size, morphology, and neural induction efficiency, which correlated with the degree of heteroplasmy. Dissociated neurons from the organoids were transferred into a 2D-culture system, which is convenient and suitable for high-throughput drug screening. The organoids also exhibited significant differences in the formation of neural networks, depending on heteroplasmy levels. Our results suggest that patient-derived iPSC-based organoid models represent a useful platform for studying MELAS mechanisms and for drug screening. This video presents comprehensive and user-friendly methods, including protocols for generating organoids and evaluating phenotypes.
|
| Volume |
(224)
|
| Published |
2025-10-10
|
| DOI |
10.3791/69303
|
| PMID |
41144335
|
| MeSH |
Brain* / pathology
Humans
Induced Pluripotent Stem Cells / cytology
Induced Pluripotent Stem Cells / pathology
MELAS Syndrome* / genetics
MELAS Syndrome* / pathology
MELAS Syndrome* / physiopathology
Neurons / cytology
Organoids* / pathology
|
| IF |
1.163
|
| Resource |
| Human and Animal Cells |
414C2(HPS4292) |
