Hair Follicle Stem Cells Regulate Apoptotic Cell Clearance to Maintain Tissue Homeostasis

Основные понятия

Hair follicle stem cells tightly regulate the clearance of apoptotic cells through a dual lipid and retinoid signaling mechanism to balance phagocytic duties with their primary function of preserving tissue integrity during homeostasis.

Аннотация

The content explores the mechanisms by which non-motile, non-professional phagocytes, such as hair follicle stem cells, can sense and eliminate dying cells while maintaining their normal tissue functions.

Key highlights:

• Billions of cells are eliminated daily from our bodies, and many epithelial and mesenchymal tissue cells can digest nearby apoptotic corpses.
• The authors exploit the cyclical bouts of tissue regeneration and degeneration during hair cycling to study this process.
• Hair follicle stem cells transiently unleash phagocytosis at the correct time and place through local molecular triggers that depend on both lipids released by neighboring apoptotic corpses and retinoids released by healthy counterparts.
• The activation of the RARγ–RXRα nuclear receptor complex enables tight regulation of apoptotic cell clearance genes and provides an effective, tunable mechanism to offset phagocytic duties against the primary stem cell function of preserving tissue integrity during homeostasis.
• The authors provide functional evidence that hair follicle stem cell-mediated phagocytosis is not simply redundant with professional phagocytes but rather has clear benefits to tissue fitness.
• The findings have broad implications for other non-motile tissue stem or progenitor cells that encounter cell death in an immune-privileged niche.

Статистика

Billions of cells are eliminated daily from our bodies.
Many epithelial and mesenchymal tissue cells can digest nearby apoptotic corpses.

Цитаты

"How these non-motile, non-professional phagocytes sense and eliminate dying cells while maintaining their normal tissue functions is unclear."
"We trace the heart of this dual ligand requirement to RARγ–RXRα, whose activation enables tight regulation of apoptotic cell clearance genes and provides an effective, tunable mechanism to offset phagocytic duties against the primary stem cell function of preserving tissue integrity during homeostasis."

Ключевые выводы из

Stem cells tightly regulate dead cell clearance to maintain tissue fitness - Nature

by Katherine S.... в www.nature.com 08-21-2024

https://www.nature.com/articles/s41586-024-07855-6

Дополнительные вопросы

What are the broader implications of this stem cell-mediated phagocytosis mechanism for tissue regeneration and homeostasis in other organ systems?

The discovery of stem cell-mediated phagocytosis in the context of tissue regeneration, as demonstrated in the hair follicle cycling model, has significant implications for other organ systems. This mechanism sheds light on how non-motile tissue stem cells can efficiently clear apoptotic cells while maintaining tissue integrity. Understanding the molecular triggers and signaling pathways involved in this process could provide insights into similar mechanisms in different tissues. This knowledge may help in developing strategies to enhance tissue regeneration and maintain homeostasis in various organ systems, especially those with high cellular turnover rates or prone to damage.

How might disruptions in this regulatory pathway contribute to the development of various pathologies, such as chronic inflammation or tissue degeneration?

Disruptions in the regulatory pathway of stem cell-mediated phagocytosis could have detrimental effects on tissue health and function, leading to the development of pathologies. Failure to efficiently clear apoptotic cells by stem cells may result in the accumulation of cellular debris, triggering inflammatory responses and potentially causing chronic inflammation. Moreover, impaired phagocytic activity of stem cells could lead to the persistence of dying cells, which may contribute to tissue degeneration and dysfunction over time. These disruptions in dead cell clearance mechanisms could disrupt tissue homeostasis and exacerbate pathological conditions in various organ systems.

Could the insights from this study inform the development of novel therapeutic approaches to enhance tissue repair and regeneration?

The insights gained from studying stem cell-mediated phagocytosis in the context of tissue regeneration offer exciting possibilities for the development of novel therapeutic approaches to enhance tissue repair and regeneration. Understanding the molecular mechanisms that regulate the balance between stem cell functions and phagocytic activity can guide the design of targeted interventions to modulate these processes. By manipulating the signaling pathways involved in stem cell-mediated phagocytosis, it may be possible to enhance the clearance of dying cells, promote tissue regeneration, and accelerate healing in damaged tissues. This knowledge could pave the way for innovative therapeutic strategies aimed at improving tissue repair outcomes in various pathological conditions.