Wnt signaling reprograms metabolism in dental pulp stem cells

Area of Science:

• Stem cell biology
• Metabolic reprogramming
• Biochemistry

Background:

• Human dental pulp stem cells (DPSCs) exhibit multipotent differentiation and share traits with pluripotent stem cells.
• Pharmacological activation of Wnt signaling can enhance DPSC stemness.

Purpose of the Study:

• To investigate the metabolic profile of DPSCs during Wnt-activated reprogramming.
• To understand how Wnt activation influences DPSC metabolism and energy status.

Main Methods:

• Short-term exposure of DPSCs to GSK3-β inhibitor BIO or WNT-3A.
• Analysis of glucose consumption, gene expression of metabolic enzymes, and mitochondrial activity.
• Nile Red staining for lipid accumulation.

Main Results:

• Wnt activation significantly increased glucose consumption and upregulated key enzymes for pyruvate and mitochondrial acetyl-CoA production.
• Mitochondrial tricarboxylic acid (TCA) cycle metabolism was activated, leading to increased reducing power and mitochondrial hyperpolarization.
• Wnt-activated DPSCs showed increased lipid storage, suggesting an energy-priming state.

Conclusions:

• Wnt-activated reprogramming profoundly remodels DPSC metabolism, with significant involvement of mitochondrial pathways.
• Metabolic reprogramming creates an energy-primed state, preparing DPSCs for high energy and biosynthesis demands.
• Enhanced stemness in DPSCs through Wnt activation is intrinsically linked to mitochondrial metabolic remodeling.