In vivo virus-free lineage tracing and live imaging reveal that NeuroD1 does not reprogram microglia into neurons
In situ glia-to-neuron conversion induced by a single transcription factor is a promising regenerative strategy for treating central nervous system injuries and neurodegenerative diseases. Previous studies reported that NeuroD1 can induce microglia-to-neuron cross-lineage conversion and improve recovery after brain injury. However, these findings remain controversial. To examine the ability of…
Recent studies have shown that a single transcription factor, NeuroD1, can potentially convert microglia into neurons, offering a promising regenerative strategy for treating brain injuries and neurodegenerative diseases. However, the findings in this area are still debated. To investigate the impact of NeuroD1 on microglia-to-neuron conversion, researchers utilized virus-free genetic lineage-tracing systems in mice.
These systems allowed them to specifically express NeuroD1 in microglia and monitor the fate of these cells over time. Additionally, they employed two-photon imaging to track the NeuroD1-expressing microglia and analyzed their transcriptional profile through single-cell RNA sequencing.
The results from these various methods consistently showed that NeuroD1-expressing cells maintained their microglia identity and were unable to transform into neurons, regardless of whether the conditions were normal or following an injury. In fact, prolonged expression of NeuroD1 led to increased microglia apoptosis in vivo. Based on these findings, the researchers conclude that NeuroD1 alone is not capable of inducing microglia-to-neuron conversion.
This study emphasizes the significance of employing robust lineage-tracing and cell fate-mapping techniques to accurately validate such transformations in situ.
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