Commensal Microbiome Promotes Hair Follicle Regeneration by Inducing Keratinocyte HIF-1α Signaling and Glutamine Metabolism

January 2023 in “ Science Advances ”

Gaofeng Wang, Evan Sweren, William Andrews, Yue Li, Junjun Chen, Y. Xue, Eric M. Wier, Martin P. Alphonse, Li Luo, Yong Miao, Ruosi Chen, Dongqiang Zeng, Sam W. Lee, Ang Li, E. Dare, Dong-Won Kim, Nathan K. Archer, Sashank Reddy, Linda M.S. Resar, Zhiqi Hu, Elizabeth A. Grice, Maureen A. Kane, Luis A. Garza

commensal microbiome hair follicle regeneration keratinocyte HIF-1α signaling glutamine metabolism wound-induced hair follicle neogenesis WIHN bacterial load topical broad-spectrum antibiotics stem cell tolerance regenerative outcomes skin microbiome HIF-1α signaling topical antibiotics

Studysummary This study found that bacterially induced metabolic changes in stem cells can enhance skin and hair follicle regeneration in both mice and humans, suggesting potential strategies for improving recovery after injury.

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The study shows that the commensal microbiome promotes hair follicle regeneration by inducing keratinocyte HIF-1α signaling and enhancing glutamine metabolism. This metabolic shift improves the regenerative capacity of skin and hair follicles following injury. Using a wound-induced hair follicle neogenesis (WIHN) model in mice, researchers found a positive correlation between bacterial load, glutamine metabolism, and regeneration. In human skin wounds, topical broad-spectrum antibiotics inhibited glutamine production and reduced healing. The findings suggest that the skin microbiome's modulation of metabolism can significantly enhance stem cell tolerance to damage and improve regenerative outcomes in both mice and humans.

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17 citations , May 2021 in “Journal of Cell Science”

In this study, the researchers discovered that specific polyamine depletion enhances stemness in hair follicle stem cells through a mechanism independent of mRNA translation.

research Bacteria Induce Skin Regeneration via IL-1β Signaling

53 citations , April 2021 in “Cell Host & Microbe”

This study found that skin microbiota, particularly in wild-type mice, promotes wound-induced hair follicle neogenesis and wound healing, highlighting the potential downsides of routine antibiotic use on skin regeneration.

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8 citations , October 2020 in “International Journal of Molecular Sciences”

This laboratory study found that nonanal, a plant scent compound, may stimulate growth factors and cell proliferation in human hair follicle dermal papilla cells, suggesting a cAMP-mediated mechanism.

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

51 citations , September 2020 in “Cell Metabolism”

This study highlights that the mammalian target of rapamycin complex 2 (mTORC2)-Akt signaling axis is essential for hair follicle stem cells to return to their niche and regenerate effectively by regulating metabolic pathways.

research IL-36α Promoted Wound-Induced Hair Follicle Neogenesis via Hair Follicle Stem/Progenitor Cell Proliferation

7 citations , September 2020 in “Frontiers in Cell and Developmental Biology”

This study found that recombinant murine IL-36α increased the number of regenerated hair follicles and accelerated wound healing in a mouse model of wound-induced hair follicle neogenesis.

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128 citations , August 2020 in “Cell stem cell”

In this study, researchers found that extrafollicular progenitors marked by Hic1 are the main contributors to reparative fibroblasts in wound repair, with potential to modulate healing outcomes through genetic and pharmacological interventions.

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47 citations , June 2019 in “Nature Communications”

This study found that self-noncoding dsRNA activates TLR3 to stimulate intrinsic retinoic acid synthesis, promoting new hair follicle formation in wounded mice and showing similar gene expression changes in humans treated with rejuvenation lasers.

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88 citations , June 2019 in “Cell reports”

This study found that activating autophagy with specific small molecules and drugs can stimulate hair growth by initiating the anagen phase in dormant hair follicles, suggesting a potential treatment for hair loss.

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202 citations , August 2017 in “Nature cell biology”

This study found that glycolytic metabolism and lactate production are crucial for hair follicle stem cell activation, and manipulating these processes can stimulate the hair cycle.

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36 citations , February 2017 in “BMC Complementary and Alternative Medicine”

In this study, Geranium sibiricum L. extract promoted hair growth in vitro with human dermal papilla cells and in vivo in mice, outperforming minoxidil by proliferating cells and stimulating growth factor expression, suggesting its potential as a hair growth treatment.

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128 citations , August 2015 in “Cell Stem Cell”

The researchers reported that dsRNA from damaged skin activates TLR3, promoting hair follicle regeneration, while TLR3-deficient animals fail to initiate this process, suggesting potential therapeutic approaches for hair neogenesis.

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237 citations , June 2013 in “Nature Medicine”

This study found that fibroblast growth factor 9, initially secreted by γδ T cells, plays a key role in modulating hair follicle regeneration in mice after skin wounds.

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829 citations , May 2007 in “Nature”

Hair follicles can regrow in wounded adult mouse skin using a process like embryo development.

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176 citations , September 2006 in “Stem Cells”

This study found that active BMP signaling prevents epithelial stem cell activation and expansion in hair follicles, while its inhibition leads to HF stem/progenitor cell overproduction and matricomas.

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1279 citations , November 2005 in “Nature Medicine”

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