In vivo virus-free lineage tracing and live imaging reveal that NeuroD1 does not reprogram microglia into neurons.

NeuroD1 does not induce microglia-to-neuron conversion in vivo, as all methods showed microglia retained their identity despite NeuroD1 expression.

• Why it matters: Understanding whether NeuroD1 can reprogram microglia into neurons is crucial for developing regenerative therapies for CNS injuries and neurodegenerative diseases, but previous findings are controversial.
• What they did: Researchers used virus-free genetic lineage-tracing, two-photon live imaging, and single-cell RNA sequencing in mice to track NeuroD1-expressing microglia over time under physiological and injury conditions, totaling multiple assessments.
• The result: NeuroD1-expressing microglia maintained their microglia identity and did not convert into neurons; instead, NeuroD1 expression promoted microglia apoptosis, indicating NeuroD1 alone is insufficient for microglia-to-neuron reprogramming.