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Identification of the core regulatory program driving NEUROD1-induced neuronal reprogramming
1Guangdong-HongKong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632, China; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-Human Primate Research, GHM Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
Cell Reports
|April 2, 2025
Summary
NEUROD1 (ND1) drives astrocyte-to-neuron conversion, a promising therapy for neurological disorders. This study reveals ND1 reshapes astrocyte chromatin, activating neurogenic genes and identifying key regulators like Hes6 for neuronal reprogramming.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Astrocyte-to-neuron (AtN) conversion is a potential therapeutic strategy for neurological disorders.
- Understanding the molecular mechanisms of neuronal reprogramming is crucial for its clinical application.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying NEUROD1 (ND1)-induced astrocyte-to-neuron conversion.
- To identify key regulators involved in this neuronal reprogramming process.
Main Methods:
- Establishment of an in vitro system using primary rat cortical astrocyte cultures.
- Application of single-cell and multiomics sequencing for comprehensive analysis.
- Chromatin landscape analysis focusing on H3K27ac modification.
Main Results:
- ND1 acts as a pioneer factor, reprogramming astrocytes into neurons by altering chromatin structure.
- ND1 induces H3K27ac modification, promoting neurogenic gene expression.
- Identification of 25 ND1 targets, including Hes6, as critical regulators of neuronal specification.
Conclusions:
- ND1 plays a pivotal role in astrocyte-to-neuron reprogramming.
- Downstream targets of ND1, such as Hes6, are key regulators in this process.
- The findings provide insights into mechanisms for developing novel regenerative therapies for neurological conditions.
Keywords:
CP: Developmental biologyCP: NeuroscienceNeuroD1chromatin remodelingepigeneticsfate commitmentmultiomicsneuronal reprogrammingpioneer factorsingle-cell sequencingtrajectoryMore Related Videos
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