Dissecting the dynamics of cell death pathways in Hirschsprung’s disease: a comparative analysis of viable and non-viable cells under proinflammatory conditions
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In brief
In brief
This study examines how cells from Hirschsprung's disease patients respond differently to inflammatory stress compared to healthy controls, using patient-derived intestinal organoids and flow cytometry. Researchers found that HSCR cells are more vulnerable to acute inflammation and show impaired adaptive responses under chronic inflammatory conditions, particularly in RIPK1-dependent apoptosis and necroptosis pathways.
- HSCR cells show increased vulnerability to acute inflammatory stress with higher cell death rates compared to controls.
- Chronic inflammation triggers adaptive survival mechanisms in both HSCR and controls, but HSCR cells show impaired responses.
- RIPK1-dependent apoptosis is significantly decreased in HSCR under acute vs chronic inflammation, unlike controls.
- Non-viable HSCR cells exhibit heightened RIPK1-dependent apoptosis under chronic inflammation vs controls.
- Patient-derived organoids reveal complex, dysregulated inflammatory responses in HSCR cell death pathways.
Written by the GCMD Library team from the article.
Abstract
Purpose
The present study explores the dynamics of cell death in Hirschsprung’s disease (HSCR) and control (CO) groups under inflammatory stress conditions.
Methods
Using flow cytometry, we analyzed intestinal colonic organoid cultures derived from the ganglionic segment of the HSCR and CO groups. Our analysis focused on the quantification of RIPK1-independent and RIPK1-dependent apoptosis, as well as necroptosis in both viable and non-viable cells under acute and chronic inflammatory stress.
Results
Our findings indicate that HSCR cells are particularly vulnerable to inflammation during acute proinflammatory stress, as evidenced by an increase in dead cells (Zombie +). Under chronic conditions, adaptive changes are observed in both HSCR and CO groups, indicating survival mechanisms. These adaptations are uniquely altered in HSCR, suggesting an impaired response to chronic inflammation. HSCR cells show significantly decreased RIPK1-dependent apoptosis in acute scenarios compared to chronic ones, unlike the CO group, implying varied responses to different inflammatory stresses. In non-viable cells, considerable changes in RIPK1-dependent apoptosis under chronic conditions in HSCR indicate a heightened inflammatory response compared to CO.
Conclusion
This research provides insights into cell death regulation in HSCR under inflammatory stress by using patient-derived organoids, underscoring the complexity of its inflammatory response.