Direct Cell Reprogramming and Phenotypic Conversion: An Analysis of Experimental Attempts to Transform Astrocytes into Neurons in Adult Animals

The central nervous system (CNS) faces challenges in repairing itself after injury or disease. One potential strategy involves converting astrocytes, a type of brain cell, into neurons. This conversion, known as AtN, aims to create new neurons directly from existing astrocytes, bypassing the need to revert cells to a pluripotent state. However, many questions remain about the effectiveness and mechanisms of this approach. This review distinguishes between direct cell conversion (using 1-2 transcription factors) and direct cell reprogramming (using ≥3 factors), aiming to promote a more mechanistic understanding of the transformation process.

• 1
  Direct cell conversion (1-2 TFs) and direct cell reprogramming (≥3 TFs or multifactor formulas) are proposed as distinct approaches to AtN, influencing the extent of epigenetic modification.
• 2
  AAV vectors are commonly used for in vivo AtN, but caution is needed due to potential mislabeling of host endogenous neurons as induced neurons.
• 3
  Small molecules can directly reprogram astrocytes into iNs, bypassing the need for exogenous TF genes and reducing the risk of tumorigenesis.
• 4
  Knockdown of PTBP1 has been reported to generate dopaminergic iNs from astrocytes to reduce motor deficits in a rodent model of Parkinson’s disease.