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Abstract
Hair follicles (HFs) are unique, multi-compartment, mini-organs that cycle through phases of active hair growth and pigmentation (anagen), apoptosis-driven regression (catagen) and relative quiescence (telogen). Anagen HFs have high demands for energy and biosynthesis precursors mainly fulfilled by aerobic glycolysis. Histochemistry reports the outer root sheath (ORS) contains high levels of glycogen. To investigate a functional role for glycogen in the HF we quantified glycogen by Periodic-Acid Schiff (PAS) histomorphometry and colorimetric quantitative assay showing ORS of anagen VI HFs contained high levels of glycogen that decreased in catagen. qPCR and immunofluorescence microscopy showed the ORS expressed all enzymes for glycogen synthesis and metabolism. Using human ORS keratinocytes (ORS-KC) and ex vivo human HF organ culture we showed active glycogen metabolism by nutrient starvation and use of a specific glycogen phosphorylase (PYGL) inhibitor. Glycogen in ORS-KC was significantly increased by incubation with lactate demonstrating a functional Cori cycle. Inhibition of PYGL significantly stimulated the ex vivo growth of HFs and delayed onset of catagen. This study defines translationally relevant and therapeutically targetable new features of HF metabolism showing that human scalp HFs operate an internal Cori cycle, synthesize glycogen in the presence of lactate and modulate their growth via PYGL activity.
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1 Queen Mary University of London, Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts & The London School of Medicine and Dentistry, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133)
2 Farjo Hair Institute, London, UK (GRID:grid.4868.2)
3 Monasterium Laboratory, Münster, Germany (GRID:grid.512318.c)
4 Monasterium Laboratory, Münster, Germany (GRID:grid.512318.c); University of Miami Miller School of Medicine, Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami, USA (GRID:grid.26790.3a) (ISNI:0000 0004 1936 8606); University of Manchester, and NIHR Biomedical Research Centre, Dermatology Research Centre, Manchester, UK (GRID:grid.5379.8) (ISNI:0000000121662407)