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Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress

DNA-damage response of cutaneous interfollicular melanocytes to fractionated radiotherapy was investigated by immunostaining of tissue sections from punch biopsies collected before, during, and after the treatment of patients for breast cancer. Our clinical assay with sterilized hair follicles, excl...

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Autores principales: Fessé, Per, Nyman, Jan, Hermansson, Ingegerd, Book, Maj-Lis, Ahlgren, Johan, Turesson, Ingela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579029/
https://www.ncbi.nlm.nih.gov/pubmed/36274944
http://dx.doi.org/10.1016/j.isci.2022.105238
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author Fessé, Per
Nyman, Jan
Hermansson, Ingegerd
Book, Maj-Lis
Ahlgren, Johan
Turesson, Ingela
author_facet Fessé, Per
Nyman, Jan
Hermansson, Ingegerd
Book, Maj-Lis
Ahlgren, Johan
Turesson, Ingela
author_sort Fessé, Per
collection PubMed
description DNA-damage response of cutaneous interfollicular melanocytes to fractionated radiotherapy was investigated by immunostaining of tissue sections from punch biopsies collected before, during, and after the treatment of patients for breast cancer. Our clinical assay with sterilized hair follicles, excluded the migration of immature melanocytes from the bulge, and highlighted interfollicular melanocytes as an autonomous self-renewing population. About thirty percent are immature. Surrounding keratinocytes induced and maintained melanocyte differentiation as long as treatment was ongoing. Concomitant with differentiation, melanocytes were protected from apoptosis by transient upregulation of Bcl-2 and CXCR2. CXCR2 upregulation also indicated the instigation of premature senescence, preventing proliferation. The stem cell factor BMI1 was constitutively expressed exclusively in interfollicular melanocytes and further upregulated upon irradiation. BMI1 prevents apoptosis, terminal differentiation, and premature senescence, allowing dedifferentiation post-treatment, by suppressing the p53/p21-and p16-mediated response and upregulating CXCR2 to genotoxic damage. The pre-treatment immature subset of interfollicular melanocytes was restored after the exposure ended.
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spelling pubmed-95790292022-10-20 Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress Fessé, Per Nyman, Jan Hermansson, Ingegerd Book, Maj-Lis Ahlgren, Johan Turesson, Ingela iScience Article DNA-damage response of cutaneous interfollicular melanocytes to fractionated radiotherapy was investigated by immunostaining of tissue sections from punch biopsies collected before, during, and after the treatment of patients for breast cancer. Our clinical assay with sterilized hair follicles, excluded the migration of immature melanocytes from the bulge, and highlighted interfollicular melanocytes as an autonomous self-renewing population. About thirty percent are immature. Surrounding keratinocytes induced and maintained melanocyte differentiation as long as treatment was ongoing. Concomitant with differentiation, melanocytes were protected from apoptosis by transient upregulation of Bcl-2 and CXCR2. CXCR2 upregulation also indicated the instigation of premature senescence, preventing proliferation. The stem cell factor BMI1 was constitutively expressed exclusively in interfollicular melanocytes and further upregulated upon irradiation. BMI1 prevents apoptosis, terminal differentiation, and premature senescence, allowing dedifferentiation post-treatment, by suppressing the p53/p21-and p16-mediated response and upregulating CXCR2 to genotoxic damage. The pre-treatment immature subset of interfollicular melanocytes was restored after the exposure ended. Elsevier 2022-09-28 /pmc/articles/PMC9579029/ /pubmed/36274944 http://dx.doi.org/10.1016/j.isci.2022.105238 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fessé, Per
Nyman, Jan
Hermansson, Ingegerd
Book, Maj-Lis
Ahlgren, Johan
Turesson, Ingela
Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
title Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
title_full Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
title_fullStr Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
title_full_unstemmed Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
title_short Human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
title_sort human cutaneous interfollicular melanocytes differentiate temporarily under genotoxic stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579029/
https://www.ncbi.nlm.nih.gov/pubmed/36274944
http://dx.doi.org/10.1016/j.isci.2022.105238
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