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Scientists discover surprising link between ancient biology and restricted human hair growth
MPC1 is expressed in the human hair follicle and MPC inhibition stalls cell cycle progression and disrupts the expression of hair follicle signaling pathway genes. A) MPC1 and PDK immunoreactivity in the human hair follicle. CTS–connective tissue sheath. DP–dermal papilla; DSC–dermal sheath cup; GL–germinative layer; HS–hair shaft; IRS–inner 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) Fluorescent EdU labeling on human hair follicle tissue sections shows how UK-5099 treatment blocks DNA replication in the hair follicle both within the bulge epithelium and hair matrix (HM). DP—dermal papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in the bulge and hair matrix following 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). Plotted line is the mean. D) Dot plot of the top 10 enriched IPA pathways following 40 μM UK-5099 treatment. Analysis conducted on 1206 genes with 2-fold change and padj <0.05. See also S3 Fig in S1 File. E) Volcano plot annotated with differentially expressed genes involved with FGF, IGF, TGFβ and Wnt signaling with an adjusted p value < 0.05 following 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 MPC inhibition stalls cell cycle progression and disrupts the expression of hair follicle signaling pathway genes. A) MPC1 and PDK immunoreactivity in the human hair follicle. CTS–connective tissue sheath. DP–dermal papilla; DSC–dermal sheath cup; GL–germinative layer; HS–hair shaft; IRS–inner 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) Fluorescent EdU labeling on human hair follicle tissue sections shows how UK-5099 treatment blocks DNA replication in the hair follicle both within the bulge epithelium and hair matrix (HM). DP—dermal papilla. Scale bar 50 μm. C) Quantitative analysis of EdU and Ki-67 in the bulge and hair matrix following 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). Plotted line is the mean. D) Dot plot of the top 10 enriched IPA pathways following 40 μM UK-5099 treatment. Analysis conducted on 1206 genes with 2-fold change and padj <0.05. See also S3 Fig in S1 File. E) Volcano plot annotated with differentially expressed genes involved with FGF, IGF, TGFβ and Wnt signaling with an adjusted p value < 0.05 following treatment of human hair follicles with 40 μM UK-5099. Credit: PLOS ONE (2024). DOI: 10.1371/journal.pone.0303742
University of Manchester scientists have linked one of the ways that cells respond to stressful conditions with restricted healthy hair growth.
The Manchester Hair Research Group team unexpectedly discovered the link in a lab experiment where they were testing a drug to see if it would cultivate 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 across life from yeast and roundworms through to humans.
The team hopes that their work in targeting the pathway might one day lead to treatments for hair loss.
Known in full as the Integrated Stress Response (ISR), it is triggered in stressful cellular conditions such as poor nutrient availability, viral infection, or when there is a buildup of misshapen proteins in cells. The ISR allows cells to put a brake on regular activities by making fewer new proteins, entering a partial stasis to adapt and deal with the stress. However, if it doesn't work, it can cause cells to die.
ISR is already the subject of great interest to scientists studying cancer, neurodegenerative disorders and aging.
Dr. Talveen Purba, Research Fellow at The University of Manchester and senior 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 found the opposite was true: Hair growth was instead blocked, as cells, including stem cells, quickly stopped dividing."
They also found signs that mitochondria were dysfunctional, and there were disruptions in how cells communicate with each other. Using a combination of experimental approaches to look more closely, 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 the microscope, it's striking how consistent the response is between hair follicles from different people."
Following on from this early-stage research, the team is now looking to better understand the broader implications of the ISR in hair follicles, and examine its activity in people with hair loss conditions.
Dr. Purba added, "We're incredibly hopeful as we believe the activation of this pathway could play an important biological role in restricting 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