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  4. HDAC Inhibitor Titration of Transcription and Axolotl Tail Regeneration

HDAC Inhibitor Titration of Transcription and Axolotl Tail Regeneration

Frontiers in Cell and Developmental Biology, 2021 · DOI: 10.3389/fcell.2021.767377 · Published: December 31, 2021

Regenerative MedicineGenetics

Simple Explanation

The study investigates how a drug, romidepsin, affects tail regeneration in axolotl embryos by influencing gene activity. Different concentrations of romidepsin were tested to find a threshold where regeneration either succeeds or fails. The researchers examined which genes were turned on or off at different drug concentrations to understand how romidepsin changes the regeneration process. They identified genes linked to oxidative stress, cell signaling, cell cycle, and cell differentiation that were affected by romidepsin. Using advanced techniques (single-nuclei RNA sequencing), they found that romidepsin's impact on gene expression occurred across various cell types, suggesting a broad mechanism regulating regeneration success or failure.

Study Duration
Not specified
Participants
Axolotl embryos
Evidence Level
Not specified

Key Findings

  • 1
    Romidepsin inhibits axolotl embryo tail regeneration above a threshold concentration.
  • 2
    Regeneration inhibitory concentrations of romidepsin increased the expression of genes associated with oxidative stress, negative regulation of cell signaling and cell cycle progression, and cellular differentiation.
  • 3
    Single-nuclei RNA-Seq revealed that key genes were altered by romidepsin in the same direction across multiple cell types.

Research Summary

This study details the concentration-dependent effects of romidepsin on transcription and regeneration in axolotl embryos. It establishes a framework for investigating small molecule mechanisms of action in regenerative biology. The research identifies specific genes whose expression is altered by romidepsin in a dose-dependent manner, linking these changes to regenerative success or failure. Key genes associate with oxidative stress, cell signaling, and cell cycle regulation. Single-nuclei RNA sequencing reveals that romidepsin's transcriptional effects are consistent across multiple cell types, suggesting a broad regulatory mechanism involving HDAC activity.

Practical Implications

Chemical Tool Development

Romidepsin can be used as a reproducible chemical tool for investigating transcription and regenerative outcomes.

Targeted Functional Studies

The study prioritizes candidate genes for functional studies, suggesting that transcriptionally modified genes are more likely to affect regeneration outcomes.

Understanding HDAC Activity

The results indicate that HDAC activity plays a central role in regulating transcription across cell types during tissue regeneration.

Study Limitations

  • 1
    Changes in transcription could reflect indirect effects of romidepsin.
  • 2
    It remains to be determined if embryo tail regeneration presents greater transcriptional plasticity than larval and adult tail regeneration.
  • 3
    Further work will be needed to determine if the high and low transcriptional states identified in this study are a general characteristic of transcription from large axolotl genes and/or the capture of nascent and steady state transcripts by snRNA-Seq.

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