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In the CNS, neurogenesis, the birth of new neurons from stem cells, is limited to the hippocampus in adults. In other regions of the brain and spinal cord, neurogenesis is almost non-existent due to inhibitory influences from neuroglia, especially oligodendrocytes, and the absence of growth-stimulating cues. The myelin produced by oligodendrocytes in the CNS inhibits neuronal regeneration. Furthermore, astrocytes proliferate rapidly after neuronal damage, forming scar tissue that physically...
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Updated: Jun 21, 2025

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A wound-induced differentiation trajectory for neurons.

Ryan E Hulett1, Carlos Rivera-López1,2, Andrew R Gehrke1

  • 1Department of Organismic and Evolutionary Biology, Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138.

Proceedings of the National Academy of Sciences of the United States of America
|July 8, 2024
PubMed
Summary

Researchers discovered how the Nuclear Factor Y (NFY) transcription factor initiates brain regeneration in the acoel worm Hofstenia miamia. NFY binding to DNA early after injury triggers the expression of genes necessary for neural cell development.

Keywords:
functional genomicsneural differentiationregenerationstem cellswound response

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Area of Science:

  • Developmental Biology
  • Regenerative Medicine
  • Neuroscience

Background:

  • Whole-body regeneration in animals allows for the de novo formation of complex organs, including brains.
  • Understanding the molecular mechanisms that initiate neural regeneration after injury is crucial for advancing regenerative medicine.

Purpose of the Study:

  • To investigate the early transcriptional events that trigger neural regeneration in the highly regenerative acoel worm, Hofstenia miamia.
  • To identify key transcription factors and progenitor cells involved in wound-induced brain formation.

Main Methods:

  • Chromatin accessibility footprinting analysis on a chromosome-scale genome assembly.
  • Single-cell transcriptome analysis.
  • Functional studies in Hofstenia miamia.

Main Results:

  • Nuclear Factor Y (NFY) transcription factor binding sites were dynamically upregulated within one hour of amputation in regenerating tail fragments.
  • NFY targets were significantly enriched for genes associated with neuronal function.
  • SoxC stem cells were identified as a potential progenitor population for neural subtypes.
  • Wound-induced SoxC expression appears to be directly regulated by NFY.

Conclusions:

  • NFY acts as an early wound-induced transcriptional regulator, initiating neural differentiation pathways.
  • This study uncovers a mechanism for the initiation of brain regeneration involving NFY and SoxC stem cells in Hofstenia miamia.