Fig. 2: Heterozygous loss of SYT13 triggers typical ALS phenotypes in 5-weeks old human MNs. | Cell Death & Disease

Fig. 2: Heterozygous loss of SYT13 triggers typical ALS phenotypes in 5-weeks old human MNs.

From: Heterozygous knockout of Synaptotagmin13 phenocopies ALS features and TP53 activation in human motor neurons

Fig. 2

A Schematic representation and sequencing of the CRISPR-Cas9 strategy to generate the SYT13+/− hiPSC line. B Rt-qPCR of the SYT13 levels in SYT13+/− and SYT13+/+ MNs. N = 6. *p < 0.05. C Representative image of DIV21 hiPSC-derived MNs positively stained against CHAT and MAP2. The expression levels of typical neuronal markers are not altered SYT13+/− MNs at this stage of culture. Scale bar 20 μm. D DIV35 SYT13+/− MNs have higher levels of SQSTM1/p62 than their isogenic controls. Scale bar 5 μm. N = 75 MNs from 3 independent differentiations. ****p < 0.0001. E Accumulation of aberrant cytosolic aggresomes is also detected in DIV35 SYT13+/− MNs. Scale bar 5 μm. N = 75 MNs from 3 independent differentiations. **p < 0.01. F SYT13+/− MNs do not show signs of TDP43 pathology. Scale bar 5 μm. Scale bar 5 μm. N = 55 MNs from 3 independent differentiations. Data are represented as the mean ± SD. G The phosphorylation levels of the stress marker Jun are significantly higher in SYT13+/− MNs than SYT13+/+ ones. Scale bar 20 μm. N = 90 MNs from 3 independent differentiations. ****p < 0.0001. H Excitatory synapses are reduced in SYT13-deficient neurons. Scale bar 3 μm. N = 30 MNs from 3 independent differentiations. ****p < 0.0001. Data are represented as the mean ± SD.

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