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Peer-reviewedCC BYELife

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

  • Xiaoyu Li1
  • Yuxin Li1
  • Yue Cao1
  • Niewen Hu1
  • Baozhi Yang2
  • Pei Ouyang1,2
  • Yuxiao Jin1
  • Shuai Gao1,2
  • Li Cao3
  • Bo Peng1,4,5
  • Yanxia Rao1,2
5 affiliations
  1. 1National Children's Medical Center, Children's Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan SANS Neuroscience Center, Fudan University, Shanghai, China.
  2. 2Department of Neurology, Zhongshan Hospital, Laboratory Animal Center, Fudan University, Shanghai, China.
  3. 3Key Laboratory of Molecular Neurobiology, Ministry of Education, Navy Military Medical University, Shanghai, China.
  4. 4Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
  5. 5MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, Fudan University, Shanghai, China.
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Abstract

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 NeuroD1 in inducing microglia-to-neuron conversion, we employed virus-free genetic lineage-tracing systems in mice to specifically induce NeuroD1 expression in microglia and track the cell fate of NeuroD1-expressing cells at multiple timepoints. Meanwhile, we longitudinally monitored NeuroD1-expressing microglia via two-photon imaging and characterized their transcriptional profile by single-cell RNA sequencing. All observations across these methods revealed that NeuroD1-expressing cells retained their microglia identity and cannot convert into neurons, no matter under physiological and injury conditions. Instead, sustained expression of NeuroD1 facilitated microglia apoptosis in vivo. Collectively, our findings provide strong evidence that NeuroD1 alone is not sufficient to induce microglia-to-neuron conversion. This study further highlights the importance of rigorous lineage-tracing and cell fate-mapping strategies for validating in situ glia-to-neuron conversion.

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Cite

BibTeXRIS
BibTeX
@article{li2026vivo,
  title = {{In vivo virus-free lineage tracing and live imaging reveal that NeuroD1 does not reprogram microglia into neurons.}},
  author = {Xiaoyu Li and Yuxin Li and Yue Cao and Niewen Hu and Baozhi Yang and Pei Ouyang and Yuxiao Jin and Shuai Gao and Li Cao and Bo Peng and Yanxia Rao},
  journal = {ELife},
  year = {2026},
  month = oct,
  doi = {10.7554/elife.112083},
  url = {https://europepmc.org/article/MED/42886204},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - In vivo virus-free lineage tracing and live imaging reveal that NeuroD1 does not reprogram microglia into neurons.
AU  - Xiaoyu Li
AU  - Yuxin Li
AU  - Yue Cao
AU  - Niewen Hu
AU  - Baozhi Yang
AU  - Pei Ouyang
AU  - Yuxiao Jin
AU  - Shuai Gao
AU  - Li Cao
AU  - Bo Peng
AU  - Yanxia Rao
PY  - 2026
DA  - 2026/10/16
JO  - ELife
DO  - 10.7554/elife.112083
UR  - https://europepmc.org/article/MED/42886204
AB  - 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 NeuroD1 in inducing microglia-to-neuron conversion, we employed virus-free genetic lineage-tracing systems in mice to specifically induce NeuroD1 expression in microglia and track the cell fate of NeuroD1-expressing cells at multiple timepoints. Meanwhile, we longitudinally monitored NeuroD1-expressing microglia via two-photon imaging and characterized their transcriptional profile by single-cell RNA sequencing. All observations across these methods revealed that NeuroD1-expressing cells retained their microglia identity and cannot convert into neurons, no matter under physiological and injury conditions. Instead, sustained expression of NeuroD1 facilitated microglia apoptosis in vivo. Collectively, our findings provide strong evidence that NeuroD1 alone is not sufficient to induce microglia-to-neuron conversion. This study further highlights the importance of rigorous lineage-tracing and cell fate-mapping strategies for validating in situ glia-to-neuron conversion.
SN  - 2050-084X
ER  -