Meis1 regulates epidermal stem cells and is required for skin tumorigenesis

Kazuhiro Okumura, Megumi Saito, Eriko Isogai, Yoshimasa Aoto, Tsuyoshi Hachiya, Yasubumi Sakakibara, Yoshinori Katsuragi, Satoshi Hirose, Ryo Kominami, Ryo Goitsuka, Takuro Nakamura, Yuichi Wakabayashi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere102111
JournalPLoS One
Volume9
Issue number7
DOIs
Publication statusPublished - 2014 Jul 11

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Stem cells
skin (animal)
carcinogenesis
stem cells
Skin
Carcinogenesis
Stem Cells
Tissue
Tumors
neoplasms
Neoplasms
epidermis (animal)
Epidermis
Blood
homeostasis
mice
Homeostasis
9,10-Dimethyl-1,2-benzanthracene
Multipotent Stem Cells
hair follicles

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Okumura, K., Saito, M., Isogai, E., Aoto, Y., Hachiya, T., Sakakibara, Y., ... Wakabayashi, Y. (2014). Meis1 regulates epidermal stem cells and is required for skin tumorigenesis. PLoS One, 9(7), [e102111]. https://doi.org/10.1371/journal.pone.0102111

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.

In: PLoS One, Vol. 9, No. 7, e102111, 11.07.2014.

Research output: Contribution to journalArticle

Okumura, K, Saito, M, Isogai, E, Aoto, Y, Hachiya, T, Sakakibara, Y, Katsuragi, Y, Hirose, S, Kominami, R, Goitsuka, R, Nakamura, T & Wakabayashi, Y 2014, 'Meis1 regulates epidermal stem cells and is required for skin tumorigenesis', PLoS One, vol. 9, no. 7, e102111. https://doi.org/10.1371/journal.pone.0102111
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. In: PLoS One. 2014 ; Vol. 9, No. 7.
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