Sox9 regulates the luminal stem/progenitor cell properties of salivary glands

Junichi Tanaka; Yo Mabuchi; Kenji Hata; Rika Yasuhara; Koki Takamatsu; Satoko Kujiraoka; Akane Yukimori; Ikuko Takakura; Hidetoshi Sumimoto; Toshiyuki Fukada; Masayuki Azuma; Haruhiko Akiyama; Riko Nishimura; Toshikazu Shimane; Kenji Mishima

doi:10.1016/j.yexcr.2019.05.030

Sox9 regulates the luminal stem/progenitor cell properties of salivary glands

Exp Cell Res. 2019 Sep 1;382(1):111449. doi: 10.1016/j.yexcr.2019.05.030. Epub 2019 May 31.

Authors

Affiliations

¹ Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, 142-8555, Japan.
² Department of Biochemistry and Biophysics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
³ Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka, 565-0871, Japan.
⁴ Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, 142-8555, Japan.
⁵ Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, 142-8555, Japan; Department of Dentistry, Jikei University School of Medicine, Tokyo, 201-8601, Japan.
⁶ Department of Medical Oncology and Cancer Center, Shiga University of Medical Science, Shiga, 520-2192, Japan.
⁷ Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, 142-8555, Japan; Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, 770-8514, Japan.
⁸ Department of Oral Medicine, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8503, Japan.
⁹ Department of Orthopaedic Surgery, School of Medicine, Gifu University, Gifu, 501-1112, Japan.
¹⁰ Head and Neck Oncology Center, Showa University, Tokyo, 142-8555, Japan.
¹¹ Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo, 142-8555, Japan. Electronic address: mishima-k@dent.showa-u.ac.jp.

PMID: 31153924
DOI: 10.1016/j.yexcr.2019.05.030

Abstract

Exocrine glands share a common morphology consisting of ductal, acinar, and basal/myoepithelial cells, but their functions and mechanisms of homeostasis differ among tissues. Salivary glands are an example of exocrine glands, and they have been reported to contain multipotent stem cells that differentiate into other tissues. In this study, we purified the salivary gland stem/progenitor cells of adult mouse salivary glands using the cell surface marker CD133 by flow cytometry. CD133⁺ cells possessed stem cell capacity, and the transplantation of CD133⁺ cells into the submandibular gland reconstituted gland structures, including functional acinar. CD133⁺ cells were sparsely distributed in the intercalated and exocrine ducts and expressed Sox9 at higher levels than CD133^- cells. Moreover, we demonstrated that Sox9 was required for the stem cell properties CD133⁺ cells, including colony and sphere formation. Thus, the Sox9-related signaling may control the regeneration salivary glands.

Keywords: CD133; Salivary gland; Sox9; Stem/progenitor cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AC133 Antigen / analysis
Adult
Aged
Animals
Cell Self Renewal
Colony-Forming Units Assay
Female
Genes, Reporter
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Middle Aged
SOX9 Transcription Factor / physiology*
Salivary Ducts / cytology
Salivary Ducts / metabolism
Stem Cell Transplantation
Stem Cells / cytology*
Stem Cells / metabolism
Submandibular Gland / cytology*
Submandibular Gland / metabolism

Substances

AC133 Antigen
PROM1 protein, human
Prom1 protein, mouse
SOX9 Transcription Factor
SOX9 protein, human
Sox9 protein, mouse