Cargando…

Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis

Previous studies have shown that Meis1 plays an important role in blood development and vascular homeostasis, and can induce blood cancers, such as leukemia. However, its role in epithelia remains largely unknown. Here, we uncover two roles for Meis1 in the epidermis: as a critical regulator of epid...

Descripción completa

Detalles Bibliográficos
Autores principales: Okumura, Kazuhiro, Saito, Megumi, Isogai, Eriko, Aoto, Yoshimasa, Hachiya, Tsuyoshi, Sakakibara, Yasubumi, Katsuragi, Yoshinori, Hirose, Satoshi, Kominami, Ryo, Goitsuka, Ryo, Nakamura, Takuro, Wakabayashi, Yuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094504/
https://www.ncbi.nlm.nih.gov/pubmed/25013928
http://dx.doi.org/10.1371/journal.pone.0102111
_version_ 1782325841308418048
author Okumura, Kazuhiro
Saito, Megumi
Isogai, Eriko
Aoto, Yoshimasa
Hachiya, Tsuyoshi
Sakakibara, Yasubumi
Katsuragi, Yoshinori
Hirose, Satoshi
Kominami, Ryo
Goitsuka, Ryo
Nakamura, Takuro
Wakabayashi, Yuichi
author_facet Okumura, Kazuhiro
Saito, Megumi
Isogai, Eriko
Aoto, Yoshimasa
Hachiya, Tsuyoshi
Sakakibara, Yasubumi
Katsuragi, Yoshinori
Hirose, Satoshi
Kominami, Ryo
Goitsuka, Ryo
Nakamura, Takuro
Wakabayashi, Yuichi
author_sort Okumura, Kazuhiro
collection PubMed
description Previous studies have shown that Meis1 plays an important role in blood development and vascular homeostasis, and can induce blood cancers, such as leukemia. However, its role in epithelia remains largely unknown. Here, we uncover two roles for Meis1 in the epidermis: as a critical regulator of epidermal homeostasis in normal tissues and as a proto-oncogenic factor in neoplastic tissues. In normal epidermis, we show that Meis1 is predominantly expressed in the bulge region of the hair follicles where multipotent adult stem cells reside, and that the number of these stem cells is reduced when Meis1 is deleted in the epidermal tissue of mice. Mice with epidermal deletion of Meis1 developed significantly fewer DMBA/TPA-induced benign and malignant tumors compared with wild-type mice, suggesting that Meis1 plays a role in both tumor development and malignant progression. This is consistent with the observation that Meis1 expression increases as tumors progress from benign papillomas to malignant carcinomas. Interestingly, we found that Meis1 localization was altered to neoplasia development. Instead of being localized to the stem cell region, Meis1 is localized to more differentiated cells in tumor tissues. These findings suggest that, during the transformation from normal to neoplastic tissues, a functional switch occurs in Meis1.
format Online
Article
Text
id pubmed-4094504
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-40945042014-07-15 Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis Okumura, Kazuhiro Saito, Megumi Isogai, Eriko Aoto, Yoshimasa Hachiya, Tsuyoshi Sakakibara, Yasubumi Katsuragi, Yoshinori Hirose, Satoshi Kominami, Ryo Goitsuka, Ryo Nakamura, Takuro Wakabayashi, Yuichi PLoS One Research Article Previous studies have shown that Meis1 plays an important role in blood development and vascular homeostasis, and can induce blood cancers, such as leukemia. However, its role in epithelia remains largely unknown. Here, we uncover two roles for Meis1 in the epidermis: as a critical regulator of epidermal homeostasis in normal tissues and as a proto-oncogenic factor in neoplastic tissues. In normal epidermis, we show that Meis1 is predominantly expressed in the bulge region of the hair follicles where multipotent adult stem cells reside, and that the number of these stem cells is reduced when Meis1 is deleted in the epidermal tissue of mice. Mice with epidermal deletion of Meis1 developed significantly fewer DMBA/TPA-induced benign and malignant tumors compared with wild-type mice, suggesting that Meis1 plays a role in both tumor development and malignant progression. This is consistent with the observation that Meis1 expression increases as tumors progress from benign papillomas to malignant carcinomas. Interestingly, we found that Meis1 localization was altered to neoplasia development. Instead of being localized to the stem cell region, Meis1 is localized to more differentiated cells in tumor tissues. These findings suggest that, during the transformation from normal to neoplastic tissues, a functional switch occurs in Meis1. Public Library of Science 2014-07-11 /pmc/articles/PMC4094504/ /pubmed/25013928 http://dx.doi.org/10.1371/journal.pone.0102111 Text en © 2014 Okumura et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Okumura, Kazuhiro
Saito, Megumi
Isogai, Eriko
Aoto, Yoshimasa
Hachiya, Tsuyoshi
Sakakibara, Yasubumi
Katsuragi, Yoshinori
Hirose, Satoshi
Kominami, Ryo
Goitsuka, Ryo
Nakamura, Takuro
Wakabayashi, Yuichi
Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis
title Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis
title_full Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis
title_fullStr Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis
title_full_unstemmed Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis
title_short Meis1 Regulates Epidermal Stem Cells and Is Required for Skin Tumorigenesis
title_sort meis1 regulates epidermal stem cells and is required for skin tumorigenesis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094504/
https://www.ncbi.nlm.nih.gov/pubmed/25013928
http://dx.doi.org/10.1371/journal.pone.0102111
work_keys_str_mv AT okumurakazuhiro meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT saitomegumi meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT isogaieriko meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT aotoyoshimasa meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT hachiyatsuyoshi meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT sakakibarayasubumi meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT katsuragiyoshinori meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT hirosesatoshi meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT kominamiryo meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT goitsukaryo meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT nakamuratakuro meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis
AT wakabayashiyuichi meis1regulatesepidermalstemcellsandisrequiredforskintumorigenesis