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Journal Article

Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle

MPS-Authors
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Kim,  C. S.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Allmeroth,  K.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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L'Hoest,  N.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Chacón-Martínez,  C. A.
Wickström – Skin Homeostasis and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Edlich-Muth,  C.
Metabolomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Giavalisco,  P.
Metabolomics, Core Facilities, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Denzel,  M. S.
Denzel – Metabolic and Genetic Regulation of Ageing, Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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Wickström,  S. A.
Wickström – Skin Homeostasis and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/32905798
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Citation

Kim, C. S., Ding, X., Allmeroth, K., Biggs, L. C., Kolenc, O. I., L'Hoest, N., et al. (2020). Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle. Cell Metab, 32(4), 629-642 e8. doi:10.1016/j.cmet.2020.08.011.


Cite as: https://hdl.handle.net/21.11116/0000-000B-3085-8
Abstract
Stem cells reside in specialized niches that are critical for their function. Upon activation, hair follicle stem cells (HFSCs) exit their niche to generate the outer root sheath (ORS), but a subset of ORS progeny returns to the niche to resume an SC state. Mechanisms of this fate reversibility are unclear. We show that the ability of ORS cells to return to the SC state requires suppression of a metabolic switch from glycolysis to oxidative phosphorylation and glutamine metabolism that occurs during early HFSC lineage progression. HFSC fate reversibility and glutamine metabolism are regulated by the mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling axis within the niche. Deletion of mTORC2 results in a failure to re-establish the HFSC niche, defective hair follicle regeneration, and compromised long-term maintenance of HFSCs. These findings highlight the importance of spatiotemporal control of SC metabolic states in organ homeostasis.