Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress

Fessé, Per; Nyman, Jan; Hermansson, Ingegerd; Book, Majlis; Ahlgren, Johan; Turesson, Ingela

doi:10.1016/j.isci.2022.105238

Cited by 3 publications

(3 citation statements)

References 92 publications

(133 reference statements)

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“…The observed elevation in serum MIA levels among our APs, compared to those engaged in an indoor profession such as office work, could potentially be attributed to their increased exposure to both ionizing (cosmic-type) and UV radiation. Indeed, these types of radiation are known to stimulate a transient activation of melanocytes [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Increased Peripheral Blood DNA Damage and Elevated Serum Levels of Melanoma Inhibitory Activity Protein: Clues to Excess Skin Cancer Risk in Airline Pilots?

Minoretti,

Liaño Riera,

Santiago Sáez

et al. 2023

Cureus

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Background and objectiveThe risk of malignant melanoma (MM) and other forms of skin cancer appears to be higher in airline pilots (APs), potentially due to their exposure to ionizing and ultraviolet (UV) radiation. We explored the possibility of increased peripheral blood DNA damage and elevated serum levels of the melanoma inhibitory activity (MIA) protein -a serological marker for MM known to be stimulated by UV radiation -in this professional group. MethodsThis was a case-control study involving 40 male APs, each of whom was age-and tenure-matched (≥5 years of service) with 40 male office workers (OWs). We assessed DNA damage in the two professional groups by performing comet and micronucleus (MN) assays on peripheral blood. Serum levels of MIA protein were quantified using an immunoassay. ResultsThe comet tail lengths and the frequency of MN were significantly higher in APs (4.57 ± 0.79 µm and 2.05 ± 0.26 per 1000 cells, respectively) than in OWs (3.81 ± 0.60 µm and 1.76 ± 0.31 per 1000 cells, respectively, both p<0.001). Furthermore, serum MIA levels were also significantly higher in APs (7.45 ± 0.95 ng/mL) than in OWs (5.78 ± 0.54 ng/mL, p<0.001). A significant positive correlation was found between comet tail lengths in APs and their serum MIA concentrations (r=0.68, p<0.01). ConclusionsThe increased burden of DNA damage and elevated serum MIA levels in APs may offer an explanation for their higher susceptibility to MM and other types of skin cancers.

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Section: Discussionmentioning

confidence: 99%

Increased Peripheral Blood DNA Damage and Elevated Serum Levels of Melanoma Inhibitory Activity Protein: Clues to Excess Skin Cancer Risk in Airline Pilots?

Minoretti,

Liaño Riera,

Santiago Sáez

et al. 2023

Cureus

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“…This lack of prematurely differentiated melanocytes, combined with the discovery that depilation causes rapid loss of ΔBmi1 McSCs, suggests that these cells reach an alternate fate. Interestingly, Fessé et al (2022) recently reported that BMI1 expression increases in self‐renewing interfollicular melanocytes when patients are treated with radiation therapy, and proposed that BMI1 functions to protect these melanocytes by suppressing p53‐mediated cell death. Therefore, BMI1 loss likely predisposes McSCs to apoptosis, instead of premature differentiation.…”

Section: Figurementioning

confidence: 99%

“…In cutaneous melanoma, we previously found that Bmi1 deletion has no impact on proliferation or tumor initiation programs, but instead specifically affects metastasis through a Cdkn2a-independent mechanism, involving epithelial-mesenchymal transition (EMT) regulation (Ferretti et al, 2016). This raises the question of whether BMI1 is involved in McSC biology, which has been proposed by others (Fessé et al, 2022;Huang & Hornyak, 2015) and, if true, whether this reflects Cdkn2a-dependent or non-canonical roles. Here, we use a mouse model, in which Bmi1 is deleted in the melanocytic lineage, to evaluate the phenotypic, cellular and molecular consequences of BMI1 loss on melanocyte biology.…”

mentioning

confidence: 98%

BMI1 is required for melanocyte stem cell maintenance and hair pigmentation

Wilson

Danielian

Salus

et al. 2023

Pigment Cell Melanoma Res

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The epigenetic repressor BMI1 plays an integral role in promoting the self‐renewal and proliferation of many adult stem cell populations, and also tumor types, primarily through silencing the Cdkn2a locus, which encodes the tumor suppressors p16Ink4a and p19Arf. However, in cutaneous melanoma, BMI1 drives epithelial‐mesenchymal transition programs, and thus metastasis, while having little impact on proliferation or primary tumor growth. This raised questions about the requirement and role for BMI1 in melanocyte stem cell (McSC) biology. Here, we demonstrate that murine melanocyte‐specific Bmi1 deletion causes premature hair greying and gradual loss of melanocyte lineage cells. Depilation enhances this hair greying defect, accelerating depletion of McSCs in early hair cycles, suggesting that BMI1 acts to protect McSCs against stress. RNA‐seq of McSCs, harvested before onset of detectable phenotypic defects, revealed that Bmi1 deletion derepresses p16Ink4a and p19Arf, as observed in many other stem cell contexts. Additionally, BMI1 loss downregulated the glutathione S‐transferase enzymes, Gsta1 and Gsta2, which can suppress oxidative stress. Accordingly, treatment with the antioxidant N‐acetyl cysteine (NAC) partially rescued melanocyte expansion. Together, our data establish a critical function for BMI1 in McSC maintenance that reflects a partial role for suppression of oxidative stress, and likely transcriptional repression of Cdkn2a.

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SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage

Lambert,

Clements,

Mukherjee

et al. 2024

Journal of Investigative Dermatology

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Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress

Cited by 3 publications

References 92 publications

Increased Peripheral Blood DNA Damage and Elevated Serum Levels of Melanoma Inhibitory Activity Protein: Clues to Excess Skin Cancer Risk in Airline Pilots?

Increased Peripheral Blood DNA Damage and Elevated Serum Levels of Melanoma Inhibitory Activity Protein: Clues to Excess Skin Cancer Risk in Airline Pilots?

BMI1 is required for melanocyte stem cell maintenance and hair pigmentation

SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage

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