Lactate dehydrogenase activity drives hair follicle stem cell activation
Open accessAbstract
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.
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LDHA expression and activity are high in HFSCs relative to other cell types in the epidermis, and promoting lactate production via MPC deletion boosts their activation.
“LDHA expression and activity are high in HFSCs relative to other cell types in the epidermis, and promoting lactate production via MPC deletion boosts their activation (208).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [208]
Deleting LDHA prevents HFSC activation and the initiation of a new hair cycle.
“Conversely, deleting LDHA prevents HFSC activation and the initiation of a new hair cycle (208).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [208]
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Flagged first, then by citations
Research works printed but not linked: 3
- [28]JS JR Nature Cell Biology in press 2017
- [36]Xie H Targeting lactate dehydrogenase--a inhibits tumorigenesis and tumor progression in mouse models of lung cancer and impacts tumor-initiating cells Cell metabolism 19 795 809 2014 24726384 PMC4096909
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“LDHA expression and activity are high in HFSCs relative to other cell types in the epidermis, and promoting lactate production via MPC deletion boosts their activation (208).”
BackgroundMihaylova, M. M., Cheng, C.-W., Cao, A. Q., Tripathi, S., Mana, M. D., Bauer-Rowe, K. E., Abu-Remaileh, M., Clavain, L., Erdemir, A., Lewis, C. A., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.04.001 · Cited by 428 · see citing works
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The force is strong with this one: metabolism (Over)powers stem cell fate
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- Authors
- Flores, A., Schell, J., Krall, A. S., Jelinek, D., Miranda, M., Grigorian, M., Braas, D., White, A. C., Zhou, J. L., Graham, N. A., Graeber, T., Seth, P., Evseenko, D., Coller, H. A., Rutter, J., Christofk, H. R., & Lowry, W. E.
- Affiliations
- University of California, Los Angeles (US)
- University of Utah (US)
- Stanford Medicine (US)
- Cornell University (US)
- University of Southern California (US)
- Beth Israel Deaconess Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Christofk, Heather R.
- Lowry, William E.
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2017-08-14
- Volume
- 19
- Issue
- 9
- Pages
- 1017-1026
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC5657543
- OpenAlex
- W2749736089
- Cited by
- 301
- References
- 36
- Citations by year
- 2026: 26 · 2025: 33 · 2024: 44 · 2023: 44 · 2022: 37 · 2021: 33 · 2020: 40 · 2019: 15 · 2018: 23 · 2017: 6
- FWCI
- 32.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UL1TR000124, 5r25ca098010-10, R25T CA098010, CA098010)
- National Cancer Institute (R25T CA098010, CA 092131, CA 098010, R25-CA098010, P50CA092131)
- National Institute of General Medical Sciences (R01GM081686, GM081686, R01GM094232, GM0866465)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR057409, R01AR070245)
- National Center for Advancing Translational Sciences
- Jonsson Comprehensive Cancer Center (UL1TR000124)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- hair follicle stem cells, lactate dehydrogenase, LDHA, glycolytic metabolism, lactic acid production, stem cell quiescence, stem cell activation, hair cycle, MPC1, c-Myc, epidermis
- MeSH terms
- Lactate Dehydrogenase 5, Acrylates, Animals, Female, Genotype, Glycolysis, Isoenzymes, L-Lactate Dehydrogenase, Male, Mice, Inbred C57BL, Phenotype, Stem Cells, Time Factors, Signal Transduction, Proto-Oncogene Proteins c-myc, Cellular Senescence, Mice, Knockout, Hair Follicle, Lactic Acid, Anion Transport Proteins, Monocarboxylic Acid Transporters, Mitochondrial Membrane Transport Proteins, Cell Proliferation
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