Table 2.
The effects of m.8344A > G mutation on the biological function of neural cells derived from MERRF-iPSCs
| M1 MERRF patient | M3 MERRF patient | |||||
|---|---|---|---|---|---|---|
| M1High | M3Med | |||||
| iPSC | iNSC | Neuron | iPSC | iNSC | Neuron | |
| m.8344A > G mutation level (%) | 41.1 ± 1.4 | 38.7 ± 1.4 | 42.5 ± 1.7 | 28.8 ± 1.1 | 27.6 ± 1.9 | 34.0 ± 2.9 |
| OXPHOSa | ||||||
| COXII | ↓ | ↓ | ↑ | ND | ||
| SDHB | ND | ↓ | ↑ | ND | ||
| ATP5A | ND | ND | ND | ND | ||
| Respiration ratea | ||||||
| Basal | ↓ | ↓ | ND | ND | ||
| ATP-coupled | ↓ | ↓ | ND | ↓ | ||
| Maximal | ↓ | ↓ | ND | ↓ | ||
| Proton leak | ND | ND | ND | ND | ||
| ROS levelsa | ND | ↑ | ↑ | ND | ↑ | ↑ |
| Antioxidant enzymesa | ||||||
| Catalase | ↑ | ↑ | ↑ | ↑ | ||
| MnSOD | ND | ↓ | ND | ND | ||
| GPx4 | ↑ | ND | ↑ | ND | ||
| Characteristic markersa | ||||||
| Stemness markers | ND | ND | ||||
| NSC specific markers | ND | ND | ||||
| Pan neuron markers | ND | ND | ||||
| Neuron cell deatha | ↑ | ↑ | ||||
| Synaptic vesicular proteinsb | ||||||
| Synaptophysin | ↓ | ↓ | ||||
| vGLUT2 | ↓ | ↓ | ||||
| Excitatory receptorsb | ||||||
| AMPARs | ↓ | ↓ | ||||
| NMDAR1 | ND | ↓ | ||||
| Neuronal function | ||||||
| Spontaneous MFRa | ↓ | ↓ | ||||
| Neuron networkb | ↓ | ↓ | ||||
| Evoked responseb | ↓ | ↓ | ||||
a: compared with isogenic control cells of subline; b: compared with M3Low neuron
AMPARs α amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, ATP5A ATP synthase α subunit, SDHB succinate dehydrogenase complex iron sulfur subunit b, COXII cytochrome c oxidase subunit II, GPx4 glutathione peroxidase 4, iNSC induced neural stem cells differentiated from iPSCs, MFR mean firing rate, MnSOD manganese-dependent superoxide dismutase, ND no difference, NMDAR1 N-methyl-d-aspartate receptor 1, vGLUT2 vesicular glutamate transporter 2. ↓, decreased; ↑, increased