Direct Neuronal Reprogramming for Disease Modeling Studies Using Patient-Derived Neurons: What Have We Learned?

Area of Science:

• Neuroscience
• Stem Cell Biology
• Genetics

Background:

• Direct neuronal reprogramming bypasses pluripotency to convert somatic cells into neurons.
• Induced neurons (iNs) can preserve donor epigenetic and aging profiles, crucial for age-related central nervous system (CNS) diseases.
• iNs offer a patient-specific approach to modeling human brain disorders.

Purpose of the Study:

• To review the literature on using iNs for modeling human brain disorders.
• To critically assess the criteria for characterizing iNs, focusing on neuronal maturity.
• To discuss the potential and challenges of iNs in biomedical applications for neurological diseases.

Main Methods:

• Literature review of studies employing direct neuronal reprogramming to generate iNs.
• Analysis of criteria used to define and characterize iN maturity and subtype specificity.
• Exploration of potential applications and challenges in disease modeling.

Main Results:

• iNs can model patient-specific neurological disorders by retaining donor characteristics.
• Key questions remain regarding iN identity, optimal conversion stages for disease assessment, and the necessity of subtype specificity.
• The field is advancing, but standardization in iN characterization is needed.

Conclusions:

• Direct neuronal reprogramming provides a powerful tool for generating patient-specific iNs for disease modeling.
• Further research is needed to standardize iN characterization and fully realize their therapeutic potential.
• iNs hold promise for advancing our understanding and treatment of neurological disorders.