MPC1 is expressed in the human hair follicle and its inhibition blocks cell cycle progression and disrupts the expression of hair follicle signaling pathway genes. A) MPC1 and PDK immunoreactivity in human hair follicle. CTS connective tissue sheath. DP–cutaneous papilla; DSC–dermal shell; GL–germinative layer; HS–hair shaft; IRS–inner root sheath; L-ORS–lower outer root sheath; SG–sebaceous gland. Regional analysis (analysis areas indicated by red dotted lines) performed on 7 anagen hair follicles from 3 donors. Mann Whitney test, p value *** 0.0006. Scale bar 50 μm. B) Fluorescent EdU labeling on tissue sections of human hair follicles shows how UK-5099 treatment blocks DNA replication in the hair follicle in both the bulge epithelium and the hair matrix (HM) . DP: cutaneous papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in the 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 to 3 donors (6 to 10 independent anagen hair follicles per condition). The line drawn is the average. D) Dot plot of the top 10 IPA pathways enriched after 40 μM UK-5099 treatment. Analysis carried out on 1206 genes with a change of a factor of 2 and a 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 its inhibition blocks cell cycle progression and disrupts the expression of hair follicle signaling pathway genes. A) MPC1 and PDK immunoreactivity in human hair follicle. CTS connective tissue sheath. DP–cutaneous papilla; DSC–dermal shell; GL–germinative layer; HS–hair shaft; IRS–inner root sheath; L-ORS–lower outer root sheath; SG–sebaceous gland. Regional analysis (analysis areas indicated by red dotted lines) performed on 7 anagen hair follicles from 3 donors. Mann Whitney test, p value *** 0.0006. Scale bar 50 μm. B) Fluorescent EdU labeling on tissue sections of human hair follicles shows how UK-5099 treatment blocks DNA replication in the hair follicle in both the bulge epithelium and the hair matrix (HM) . DP: cutaneous papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in the 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 to 3 donors (6 to 10 independent anagen hair follicles per condition). The line drawn is the average. D) Dot plot of the top 10 IPA pathways enriched after 40 μM UK-5099 treatment. Analysis carried out on 1206 genes with a change of a factor of 2 and a 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
Scientists from the University of Manchester have linked one of the ways cells respond to stressful conditions to restricted healthy hair growth.
The Manchester Hair Research Group team unexpectedly discovered the link during a lab experiment where they were testing a drug to see if it could grow human scalp hair follicles in a dish. The study inadvertently led to a link to the cellular stress response, an ancient biological mechanism that occurs throughout life, from yeast and roundworms to humans.
The study is published in PLOS ONE.
The team hopes their work targeting this pathway could one day lead to treatments for hair loss.
Known in its entirety as the integrated stress response (ISR), it is triggered under stressful cellular conditions such as poor nutrient availability, viral infection, or accumulation of distorted proteins in cells. ISR allows cells to curb their regular activities by producing fewer new proteins and entering partial stasis to adapt and cope with stress. However, if this doesn’t work, it can lead to cell death.
ISR is already attracting great interest from scientists studying cancer, neurodegenerative diseases and aging.
Dr Talveen Purba, a researcher at the University of Manchester and lead author of the study, said: “We were testing a drug that targets metabolism in human hair follicles to influence how cells generate energy, which, based on the work of others, we expected to stimulate stem cells. However, we discovered the opposite: hair growth was blocked because cells, including stem cells, quickly stopped dividing.
They also discovered signs of mitochondrial dysfunction and disruptions in the way cells communicate with each other. Using a combination of experimental approaches to take a closer look, the team found signs that ISR activation was to blame.
Derek Pye, chief technician 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 of different people. »
Building on this early research, the team is now seeking to better understand the broader implications of ISR in hair follicles and examine its activity in people suffering from hair loss.
Dr Purba added: “We are extremely optimistic because we believe that activating this pathway could play an important biological role in restricting hair growth in people with hair loss, 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
Journal information:
PLoS ONE