Apoptotic cells represent a dynamic stem cell niche governing proliferation and tissue regeneration

Area of Science:

• Cell Biology
• Developmental Biology
• Regenerative Medicine

Background:

• Stem cells (SCs) are crucial for tissue homeostasis and repair.
• Mechanisms regulating SC elimination and compensatory proliferation upon loss are not fully understood.

Purpose of the Study:

• To investigate the role of Caspase-9 in hair follicle stem cell (HFSC) apoptosis and clearance.
• To elucidate the molecular mechanisms by which apoptotic cells influence SC behavior and tissue regeneration.

Main Methods:

• Genetic deletion of Caspase-9 in mouse HFSCs.
• Analysis of apoptotic markers (cleaved caspase-3) and cell clearance.
• Assessment of Wnt3 signaling and proliferation pathways.
• Evaluation of wound repair and hair follicle regeneration in Casp9-deficient mice.

Main Results:

• Caspase-9 deletion in HFSCs delays apoptosis and impairs their clearance due to a caspase-3/caspase-9 feedforward loop.
• Casp9-deficient HFSCs remain in an apoptotic-engaged state, acting as signaling centers.
• A caspase-3/Dusp8/p38 module induces Wnt3 release from apoptotic HFSCs, promoting proliferation.
• Caspase-9 deletion accelerates wound repair and de novo hair follicle regeneration.

Conclusions:

• Apoptotic cells create a dynamic niche that signals for SC proliferation and tissue regeneration.
• The caspase-3/caspase-9 loop is essential for proper apoptotic cell clearance.
• Targeting apoptotic cell signaling pathways may enhance regenerative processes.