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Published on: May 20, 2020
Cell death modalities modulate inflammatory and regenerative programs in zebrafish sensory organs
Daniela Münch1, Shiyuan Chen1, Elizabeth Ellis1,2
1Stowers Institute for Medical Research, Kansas City, MO, USA.
Abstract:
Regeneration is triggered by cells dying due to various types of injuries. However, it remains unclear whether different types of cell death elicit distinct regeneration responses. Here, we systematically profile dynamic transcriptional responses of macrophages and lateral line cells to different cell death modalities during zebrafish sensory hair cell regeneration. We show that chemogenetically induced programmed hair cell death triggers a diminished inflammatory response compared to pharmacologically induced cell lysis, characterized by minimal neutrophil recruitment, distinct transcriptional profiles in phagocytosing macrophages and reduced expression of injury-responsive genes in lateral line cells. Nevertheless, regeneration ultimately converges on a shared set of regeneration-specific genes. Importantly, preventing immune cell recruitment enhances injury-induced support cell proliferation in response to programmed, but not unprogrammed cell death, highlighting cell death-dependent regenerative outcomes following immune cell inhibition. Our findings demonstrate that different forms of cell death trigger distinct molecular events, with implications for tailoring regenerative therapies to specific injury contexts.
Insights
Different cell death types trigger distinct regeneration pathways. Programmed cell death causes less inflammation than lysis, impacting immune cells and regeneration outcomes, crucial for future therapies.
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.
