Department of Neurosurgery, Jinshan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200032, China.
Co-Innovation Center of Neuroregeneration, Nantong University, 226001, Nantong, China.
Mol Brain. 2022 Apr 5;15(1):31. doi: 10.1186/s13041-022-00912-z.
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.
NeuroD1 诱导的小胶质细胞向神经元的转变存在争议。最近，我们在《神经元》杂志上发表了一篇论文，证明 NeuroD1 不能诱导小胶质细胞向神经元的跨谱系转化。在《神经元》杂志的同一期上，Matsuda 等人观察到了“NeuroD1 诱导的小胶质细胞向神经元的转化”表型，他们对我们的研究做出了回应。他们声称，由于我们实验中 NeuroD1 的表达效率较低，我们未能在体外观察到 NeuroD1 诱导的小胶质细胞向神经元的转化。他们认为，我们研究中的 NeuroD1 上调幅度约为 200 倍（与对照相比），而 Nakashima 实验室的上调幅度为 3000 倍，是我们的 15 倍。事实上，并非如此。我们比较了原始论文中的表达水平，发现我们的 NeuroD1 表达水平与 Matsuda 等人的水平相当（《神经元》101:472-485.e477, 2019），甚至更高。因此，未能观察到 NeuroD1 诱导的小胶质细胞向神经元的转化不能归因于低表达水平。
