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Regeneration is the process of restoring injured or lost tissues, organs, or body parts. While simpler organisms generally show greater ability to regenerate their whole body, few complex animals show similarly exceptional regeneration. For example, planarian flatworms have a unique regenerative potential making them a popular study organism among biologists to understand the mechanisms of whole body regeneration. Other organisms, such as hydra, also show extreme regeneration potential;...
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Regeneration and repair processes are critical in healing damages caused by injury, disease, and aging. In regeneration, the damaged tissue is entirely replaced with new growth that restores the original architecture and function. In contrast, tissue repair usually results in a fixed tissue architecture involving scar formation. Scars generally do not reestablish tissue function and may also exhibit structural abnormalities at the injury site.
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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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m6 A promotes planarian regeneration.

Guanshen Cui1,2,3, Jia-Yi Zhou1, Xin-Yang Ge1,2

  • 1CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, China.

Cell Proliferation
|April 21, 2023
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Summary

RNA N6 -methyladenosine (m6 A) modification is crucial for planarian whole-body regeneration. Depleting wtap, an m6 A regulator, halts regeneration by affecting cell communication and cell cycle, highlighting m6 A

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Area of Science:

  • * Molecular Biology
  • * Developmental Biology
  • * Regenerative Medicine

Background:

  • * Regeneration is the biological process of regrowing damaged tissues or organs.
  • * Planarians are ideal models for studying regeneration due to their extensive stem cell populations.
  • * RNA N6 -methyladenosine (m6 A) modification influences stem cell functions but its role in whole-organism regeneration is unclear.

Purpose of the Study:

  • * To investigate the role of m6 A modification in planarian whole-body regeneration.
  • * To identify the molecular mechanisms by which m6 A regulates regeneration.

Main Methods:

  • * Depletion of the m6 A methyltransferase regulatory subunit wtap in planarians.
  • * Single-cell RNA sequencing (scRNA-seq) to analyze gene expression changes.
  • * Functional rescue experiments by depleting specific m6 A-modified transcripts.

Main Results:

  • * Depletion of wtap abolished planarian regeneration, impacting cell-cell communication and cell cycle genes.
  • * scRNA-seq revealed that wtap knockdown induced neural progenitor-like cells expressing the grn ligand.
  • * Depleting grn, cdk9, or cdk7 partially rescued regeneration defects caused by wtap depletion.

Conclusions:

  • * m6 A modification, regulated by wtap, is essential for planarian whole-organism regeneration.
  • * m6 A likely controls regeneration by modulating cell communication and cell cycle pathways.
  • * Targeting m6 A pathways offers potential therapeutic strategies for regenerative medicine.