Abstract
Although normally dormant, hair follicle stem cells (HFSCs) quickly become activated to divide during a new hair cycle. The quiescence of HFSCs is known to be regulated by a number of intrinsic and extrinsic mechanisms. Here we provide several lines of evidence to demonstrate that HFSCs utilize glycolytic metabolism and produce significantly more lactate than other cells in the epidermis. Furthermore, lactate generation appears to be critical for the activation of HFSCs as deletion of lactate dehydrogenase (Ldha) prevented their activation. Conversely, genetically promoting lactate production in HFSCs through mitochondrial pyruvate carrier 1 (Mpc1) deletion accelerated their activation and the hair cycle. Finally, we identify small molecules that increase lactate production by stimulating Myc levels or inhibiting Mpc1 carrier activity and can topically induce the hair cycle. These data suggest that HFSCs maintain a metabolic state that allows them to remain dormant and yet quickly respond to appropriate proliferative stimuli.
MeSH terms
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Acrylates / pharmacology
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Animals
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Anion Transport Proteins / antagonists & inhibitors
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Anion Transport Proteins / genetics
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Anion Transport Proteins / metabolism
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Cell Proliferation* / drug effects
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Cellular Senescence* / drug effects
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Female
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Genotype
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Glycolysis* / drug effects
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Hair Follicle / cytology
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Hair Follicle / drug effects
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Hair Follicle / enzymology*
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Isoenzymes / deficiency
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Isoenzymes / genetics
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Isoenzymes / metabolism
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L-Lactate Dehydrogenase / deficiency
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L-Lactate Dehydrogenase / genetics
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L-Lactate Dehydrogenase / metabolism*
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Lactate Dehydrogenase 5
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Lactic Acid / metabolism*
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Male
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Mice, Inbred C57BL
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Mice, Knockout
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Mitochondrial Membrane Transport Proteins / antagonists & inhibitors
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Mitochondrial Membrane Transport Proteins / genetics
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Mitochondrial Membrane Transport Proteins / metabolism
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Monocarboxylic Acid Transporters
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Phenotype
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Proto-Oncogene Proteins c-myc / metabolism
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Signal Transduction
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Stem Cells / drug effects
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Stem Cells / enzymology*
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Time Factors
Substances
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Acrylates
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Anion Transport Proteins
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Isoenzymes
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MPC1 pyruvate carrier protein, mouse
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Mitochondrial Membrane Transport Proteins
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Monocarboxylic Acid Transporters
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Myc protein, mouse
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Proto-Oncogene Proteins c-myc
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Lactic Acid
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2-cyano-3-(1-phenylindol-3-yl)acrylate
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L-Lactate Dehydrogenase
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Lactate Dehydrogenase 5