Cell death modalities modulate inflammatory and regenerative programs in zebrafish sensory organs.

Area of Science:

• Regenerative Medicine
• Cell Biology
• Immunology

Background:

• Cell death is a known trigger for tissue regeneration.
• The specific impact of different cell death modalities on regeneration remains largely unexplored.

Purpose of the Study:

• To investigate how distinct cell death types influence the molecular and cellular responses during zebrafish sensory hair cell regeneration.
• To compare the regenerative outcomes following programmed cell death versus cell lysis.

Main Methods:

• Systematic transcriptional profiling of macrophages and lateral line cells.
• Chemogenetic and pharmacological induction of specific cell death modalities in zebrafish.
• Analysis of immune cell recruitment and gene expression patterns.

Main Results:

• Programmed cell death induced a weaker inflammatory response than cell lysis, with less neutrophil recruitment and altered macrophage gene expression.
• Lateral line cells showed reduced injury-responsive gene expression following programmed cell death.
• Despite initial differences, regeneration converged on a common set of regeneration-specific genes.
• Inhibition of immune cell recruitment enhanced support cell proliferation after programmed cell death, but not lysis.

Conclusions:

• Different cell death modalities elicit distinct molecular and inflammatory responses during regeneration.
• Immune cell involvement significantly modulates regenerative outcomes in a cell death-dependent manner.
• Findings suggest potential for tailoring regenerative therapies based on specific injury-induced cell death types.