Mitochondrial aerobic respiration is activated during hair follicle stem cell differentiation, and its dysfunction retards hair regeneration

Abstract

Background. Emerging research revealed the essential role of mitochondria in regulating stem/progenitor cell differentiation of neural progenitor cells, mesenchymal stem cells and other stem cells through reactive oxygen species (ROS), Notch or other signaling pathway. Inhibition of mitochondrial protein synthesis results in hair loss upon injury. However, alteration of mitochondrial morphology and metabolic function during hair follicle stem cells (HFSCs) differentiation and how they affect hair regeneration has not been elaborated upon.Methods. We compared the difference in mitochondrial morphology and activity between telogen bulge cells and anagen matrix cells. Expression levels of mitochondrial ROS and superoxide dismutase 2 (SOD2) were measured to evaluate redox balance. In addition, the level of pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase (PDH) were estimated to present the change in energetic metabolism during differentiation. To explore the effect of the mitochondrial metabolism on regulating hair regeneration, hair growth was observed after application of a mitochondrial respiratory inhibitor upon hair plucking.Results. During HFSCs differentiation, mitochondria became elongated with more abundant organized cristae and showed higher activity in differentiated cells. SOD2 was enhanced for redox balance with relatively stable ROS levels in differentiated cells. PDK increased in HFSCs while differentiated cells showed enhanced PDH, indicating that respiration switched from glycolysis to oxidative phosphorylation during differentiation. Inhibiting mitochondrial respiration in differentiated hair follicle cells upon hair plucking repressed hair regeneration in vivo.Conclusions. Upon HFSCs differentiation, mitochondria are elongated with more abundant cristae and show higher activity, accompanying with activated aerobic respiration in differentiated cells for higher energy supply. Also, dysfunction of mitochondrial respiration delays hair regeneration upon injury.

Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells

“…This finding supports the prevailing view that differentiation is energetically demanding for stem cells, and thus causes increased ATP production through increased oxidative phosphorylation [29][30][31][32] . It is further noteworthy that osteoblasts, as programmed from MSCs by the NSQ surface, are slow growing cells 19,33,34 .…”

Anin situatlas of mitochondrial DNA in mammalian tissues reveals high content in stem/progenitor cells

“…anagen cells than telogen cells. 57 In the gastrointestinal tract, the human ( Figure 9 ) and mouse small intestine showed more mtDNA signals in the crypts, where the stem cells and transient amplifying/proliferative compartment cells are located, compared to the villus tips ( Figure 9 ). A similar pattern was present in the colon of both mouse and human, and mouse stomach, where the stem/proliferative cells in the isthmus showed higher mtDNA signals than the surface or deeper glands ( Supplemental Figure 7).…”

Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

“…Examples include hematopoietic stem cells in the bone marrow [11], intestinal crypt stem cells [12] and hair follicle stem cells [13]. Muscle satellite stem cells (MuSCs) illustrate how dynamic metabolic regulation can be under different physiological conditions.…”