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Publication : NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming.

First Author  Rao Y Year  2021
Journal  Neuron Volume  109
Issue  24 Pages  4094-4108.e5
PubMed ID  34875233 Mgi Jnum  J:328597
Mgi Id  MGI:6877237 Doi  10.1016/j.neuron.2021.11.008
Citation  Rao Y, et al. (2021) NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming. Neuron 109(24):4094-4108.e5
abstractText  The regenerative capacity of neurons is limited in the central nervous system (CNS), with irreversible neuronal loss upon insult. In contrast, microglia exhibit extraordinary capacity for repopulation. Matsuda et al. (2019) recently reported NeuroD1-induced microglia-to-neuron conversion, aiming to provide an "unlimited" source to regenerate neurons. However, the extent to which NeuroD1 can exert cross-lineage reprogramming of microglia (myeloid lineage) to neurons (neuroectodermal lineage) is unclear. In this study, we unexpectedly found that NeuroD1 cannot convert microglia to neurons in mice. Instead, NeuroD1 expression induces microglial cell death. Moreover, lineage tracing reveals non-specific leakage of similar lentiviruses as previously used for microglia-to-neuron conversion, which confounds the microglia-to-neuron observation. In summary, we demonstrated that NeuroD1 cannot induce microglia-to-neuron cross-lineage reprogramming. We here propose rigid principles for verifying glia-to-neuron conversion. This Matters Arising paper is in response to Matsuda et al. (2019), published in Neuron.
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