MPC1 is expressed in the human hair follicle, and inhibition of MPC slows cell cycle progression and disrupts the expression of hair follicle signaling pathway genes. A) MPC1 and PDK immunoreactivity in a human hair follicle. CTS – connective tissue sheath. DP – dermal papilla; DSC – dermal capsule cup; GL–germinative layer; HS – hair shaft; IRS – internal root sheath; L-ORS – lower outer root sheath; SG – sebaceous gland. Regional analysis (zones of analysis indicated by red dashed lines) performed on 7 anagen hair follicles from 3 donors. Mann Whitney test, p value*** 0.0006. Scale bar 50 μm. B) EdU fluorescence labeling of human hair follicle tissue sections shows how UK-5099 treatment blocks hair follicle DNA replication in both the bulging epithelium and the hair matrix (HM). DP – dermal papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in bulge and hair matrix after UK-5099 treatment. Ordinary one-way Anova with multiple comparisons. EdU analyses: Adjusted p-values ​​*** 0.0002, **** <0.0001. Ki-67 analyses: Adjusted p-values** 0.0018; *** 0.0006; **** <0.0001. N = 2–3 donors (6–10 independent anagen hair follicles per condition). The plotted line is the average. D) Scatter plot of the top 10 IPA-enriched lanes after treatment with 40 µM UK-5099. Analysis performed on 1206 genes with 2-fold change and padj <0.05. See also Figure S3 in File S1. E) Volcano plot annotated with differentially expressed genes involved in FGF, IGF, TGFβ and Wnt signaling with adjusted p value < 0.05 after treatment of human hair follicles with 40 µM UK-5099. Credit: PLOS ONE (2024). DOI: 10.1371/journal.pone.0303742
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MPC1 is expressed in the human hair follicle, and inhibition of MPC slows cell cycle progression and disrupts the expression of hair follicle signaling pathway genes. A) MPC1 and PDK immunoreactivity in a human hair follicle. CTS – connective tissue sheath. DP – dermal papilla; DSC – dermal capsule cup; GL–germinative layer; HS – hair shaft; IRS – internal root sheath; L-ORS – lower outer root sheath; SG – sebaceous gland. Regional analysis (zones of analysis indicated by red dashed lines) performed on 7 anagen hair follicles from 3 donors. Mann Whitney test, p value*** 0.0006. Scale bar 50 μm. B) EdU fluorescence labeling of human hair follicle tissue sections shows how UK-5099 treatment blocks hair follicle DNA replication in both the bulging epithelium and the hair matrix (HM). DP – dermal papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in bulge and hair matrix after UK-5099 treatment. Ordinary one-way Anova with multiple comparisons. EdU analyses: Adjusted p-values ​​*** 0.0002, **** <0.0001. Ki-67 analyses: Adjusted p-values** 0.0018; *** 0.0006; **** <0.0001. N = 2–3 donors (6–10 independent anagen hair follicles per condition). The plotted line is the average. D) Scatter plot of the top 10 IPA-enriched lanes after treatment with 40 µM UK-5099. Analysis performed on 1206 genes with 2-fold change and padj <0.05. See also Figure S3 in File S1. E) Volcano plot annotated with differentially expressed genes involved in FGF, IGF, TGFβ and Wnt signaling with adjusted p value < 0.05 after treatment of human hair follicles with 40 µM UK-5099. Credit: PLOS ONE (2024). DOI: 10.1371/journal.pone.0303742
Researchers at the University of Manchester have linked one of the ways cells respond to stressful conditions to limited healthy hair growth.
The Manchester Hair Research Group team unexpectedly discovered the link in a laboratory experiment where they tested the drug to see if it would cultivate hair follicles on a human scalp in a dish. The study inadvertently led to a link to the cellular stress response—an ancient biological mechanism that occurs across life from yeast and roundworms to humans.
The study is published in PLOS ONE.
The team hopes their work targeting the pathway may one day lead to a cure for hair loss.
Fully known as the integrated stress response (ISR), it is triggered by stressful cellular conditions, such as poor nutrient availability, viral infection, or when misfolded proteins accumulate in cells. ISR allows cells to put the brakes on regular activities by making fewer new proteins, entering partial stagnation to adapt and deal with stress. But if it doesn’t work, it can cause cells to die.
ISR is already of great interest to scientists studying cancer, neurodegenerative disorders, and aging.
Dr. Talveen Purba, a researcher at the University of Manchester and lead author of the study, said: “We tested a drug that targets metabolism in human hair follicles to affect how cells generate energy, which – based on the work of others – we expected we were going to stimulate stem cells, but we found that the opposite was true: hair growth was instead blocked because cells, including stem cells, quickly stopped dividing.
They also found signs that the mitochondria were dysfunctional and there was a disruption in communication between the cells. Using a combination of experimental approaches to take a closer look, the team found signs that ISR activation was to blame.
Derek Pye, chief engineer of the research group and co-author of the study, said: “When we look at hair follicles under a microscope, it is striking how consistent the response is between hair follicles from different people.”
Following on from this early-stage research, the team is now seeking to better understand the wider implications of ISR in hair follicles and investigate its activity in people with hair loss conditions.
Dr. Purba added: “We are incredibly confident because we believe that activating this pathway could play an important biological role in limiting hair growth in people with hair loss conditions, meaning that targeting it could lead to new treatments.”
More information:
Derek Pye et al, Activation of the integrated stress response in human hair follicles, PLOS ONE (2024). DOI: 10.1371/journal.pone.0303742
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PLoS ONE