Positional information modulates transient regeneration-activated cell states during vertebrate appendage...

Area of Science:

• Developmental Biology
• Regenerative Medicine
• Cell Biology

Background:

• Organismal injury necessitates tissue restoration, but the mechanisms by which positional information is conveyed to guide regeneration are not fully understood.
• Amputation site influences appendage regeneration speed, highlighting the need to elucidate underlying positional signaling pathways.

Purpose of the Study:

• To investigate the mechanisms of positional information transfer during caudal fin regeneration in the African killifish (Nothobranchius furzeri).
• To identify cellular states and molecular players involved in modulating regeneration based on amputation position.

Main Methods:

• Comparative analysis of tissue dynamics during caudal fin regeneration.
• Single-cell RNA sequencing to identify cell states and gene expression profiles.
• CRISPR-Cas9 gene editing to assess the function of extracellular matrix modifiers.

Main Results:

• Regeneration exhibits position-specific differences in cell proliferation.
• A transient regeneration-activated cell state (TRACS) in the basal epidermis was identified, its amplification correlating with amputation position.
• TRACS express extracellular matrix (ECM) components and modifiers; deletion of SQSTM1 enhanced regeneration of distal injuries, uncoupling growth rate from amputation position.

Conclusions:

• Basal epidermis TRACS transduce positional information to the regenerating blastema via ECM remodeling.
• The rate of regeneration growth can be modulated independently of amputation site.
• This study provides insights into the fundamental mechanisms of positional signaling in tissue regeneration.