MPC1 is expressed in the human hair follicle, and inhibition of MPC arrests cell cycle progression and disrupts gene expression of the hair follicle signaling pathway. A) MPC1 and PDK immunoreactivity in human hair follicle. CTS–connective tissue sheath. DP–dermal papilla; DSC–dermal sheath; GL–germinal layer; HS–hair; IRS–internal root sheath; L-ORS–lower outer root sheath; SG – sebaceous gland. Regional analysis (areas 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) Fluorescent EdU labeling of human hair follicle tissue sections shows how UK-5099 treatment blocks hair follicle DNA replication in both the protruding epithelium and the hair matrix (HM). DP—dermal papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in the hair follicle and matrix after UK-5099 treatment. Simple one-way Anova with multiple comparisons. EdU analyses: Adjusted p-values *** 0.0002, **** <0.0001. Ki-67 assays: Adjusted p-values ** 0.0018; *** 0.0006; **** <0.0001. N = 2–3 donors (6–10 independent anagen hair follicles per condition). The dashed line is the mean value. D) Dot plot of the top 10 enriched IPA pathways 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: PLUS ONE (2024). DOI: 10.1371/journal.pone.0303742
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MPC1 is expressed in the human hair follicle, and inhibition of MPC arrests cell cycle progression and disrupts gene expression of the hair follicle signaling pathway. A) MPC1 and PDK immunoreactivity in human hair follicle. CTS–connective tissue sheath. DP–dermal papilla; DSC–dermal sheath; GL–germinal layer; HS–hair; IRS–internal root sheath; L-ORS–lower outer root sheath; SG – sebaceous gland. Regional analysis (areas 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) Fluorescent EdU labeling of human hair follicle tissue sections shows how UK-5099 treatment blocks hair follicle DNA replication in both the protruding epithelium and the hair matrix (HM). DP—dermal papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in the hair follicle and matrix after UK-5099 treatment. Simple one-way Anova with multiple comparisons. EdU analyses: Adjusted p-values *** 0.0002, **** <0.0001. Ki-67 assays: Adjusted p-values ** 0.0018; *** 0.0006; **** <0.0001. N = 2–3 donors (6–10 independent anagen hair follicles per condition). The dashed line is the mean value. D) Dot plot of the top 10 enriched IPA pathways 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: PLUS ONE (2024). DOI: 10.1371/journal.pone.0303742
Scientists from the University of Manchester have linked one of the ways in which cells respond to stressful conditions to the limited growth of healthy hair.
The Manchester Hair Research Group team unexpectedly discovered the link in a laboratory experiment where they tested a drug to see if it would grow human scalp hair follicles in a dish. The study inadvertently led to a link to the cellular stress response, an ancient biological mechanism found in all life from yeast and roundworms to humans.
The study was published in PLUS ONE.
The team hopes their work in guiding the way could one day lead to treatments for hair loss.
Known in its entirety as the integrated stress response (ISR), it is triggered by stressful cellular conditions such as poor nutrient availability, viral infection, or when there is an accumulation of misfolded proteins in cells. ISR allows cells to put the brakes on regular activities, producing fewer new proteins, going into a partial shutdown to adapt and cope with stress. However, if it doesn’t work, it can lead to cell death.
ISR is already of great interest to scientists studying cancer, neurodegenerative diseases, and aging.
Dr Talveen Purba, research fellow at the University of Manchester and senior author of the study, said: “We tested a drug that targets the metabolism in human hair follicles to affect the way cells generate energy, which – on building on the work of others—we expected to stimulate stem cells, but found the opposite was true: instead, hair growth was blocked because cells, including stem cells, quickly stopped dividing.”
They also found signs that mitochondria were malfunctioning and there was a disruption 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’s striking how consistent the response is between hair follicles from different people.”
Following this early-stage research, the team now aims to better understand the wider implications of ISR in hair follicles and to study its activity in people with hair loss conditions.
Dr Purba added: “We are extremely hopeful as we believe that activating this pathway may 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 info:
Derek Pye et al, Activation of the integrated stress response in human hair follicles, PLUS ONE (2024). DOI: 10.1371/journal.pone.0303742
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