Failure of observing NeuroD1-induced microglia-to-neuron conversion in vitro is not attributed to the low NeuroD1 expression level

NeuroD1-induced microglia-to-neuron conversion is hotly debated. Recently, we published a paper in Neuron demonstrating that NeuroD1 cannot induce microglia-to-neuron cross-lineage conversion. In the same issue of Neuron, Matsuda et al., who observed the NeuroD1-induced microglia-to-neuron conversion phenotype, responded to our study. They claimed that we failed to observe NeuroD1-induced microglia-to-neuron conversion in vitro due to the low NeuroD1 expression efficiency in our experiment. They argued that the NeuroD1 upregulation in our study was around 200-fold (vs. control), whereas the upregulation in Nakashima lab was 3000-fold, 15 times higher than ours. In fact, this is not true. We compared the expression level from the original paper and found that our NeuroD1 expression level was comparable to that of Matsuda et al. (Neuron 101:472-485.e477, 2019), or even higher. Therefore, the failure of observing NeuroD1-induced microglia-to-neuron conversion cannot be attributable to the low expression level.

Automated summary

The debate on NeuroD1-induced microglia-to-neuron conversion has recently been addressed. A study published in Neuron demonstrates that NeuroD1 is unable to induce such conversion. However, researchers who observed the conversion responded, claiming that the failure to observe it in vitro was due to low NeuroD1 expression efficiency. The authors of the original study refute this claim, stating that their NeuroD1 expression level was comparable to the other study, or even higher.