title: Maintenance of sweat glands by stem cells located in the acral epithelium.
abstract: The skin is responsible for a variety of physiological functions and is critical for wound healing and repair. Therefore, the regenerative capacity of the skin is important. However, stem cells responsible for maintaining the acral epithelium had not previously been identified. In this study, we identified the specific stem cells in the acral epithelium that participate in the long-term maintenance of sweat glands, ducts, and interadnexal epidermis and that facilitate the regeneration of these structures following injury. Lgr6-positive cells and Bmi1-positive cells were found to function as long-term multipotent stem cells that maintained the entire eccrine unit and the interadnexal epidermis. However, while Lgr6-positive cells were rapidly cycled and constantly supplied differentiated cells, Bmi1-positive cells were slow to cycle and occasionally entered the cell cycle under physiological conditions. Upon irradiation-induced injury, Bmi1-positive cells rapidly proliferated and regenerated injured epithelial tissue. Therefore, Bmi1-positive stem cells served as reservoir stem cells. Lgr5-positive cells were rapidly cycled and maintained only sweat glands; therefore, we concluded that these cells functioned as lineage-restricted progenitors. Taken together, our data demonstrated the identification of stem cells that maintained the entire acral epithelium and supported the different roles of three cellular classes.
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan; Department of Dermatology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohe
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan; Third Department of Internal Medicine, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan; Department of Surgery, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yanai
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan; Department of Urology and Andrology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komai
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan; Department of Pediatrics, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Omachi
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Kanno
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Kiyomichi
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ishigaki
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Saiga
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan; Third Department of Internal Medicine, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nakamura
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan; Department of Urology and Andrology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Ohsugi
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tokuyama
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Naho
authors.initials: N
authors.lastname: Atsumi
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hisha
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Keiki
authors.initials: K
authors.lastname: Kumano
authors.affiliation: Department of Dermatology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Yamazaki
authors.affiliation: Department of Dermatology, Kansai Medical University, Osaka 573-1010, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Stem Cell Pathology, Kansai Medical University, Osaka 573-1010, Japan. Electronic address: hueno@hirakata.kmu.ac.jp.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000818:Animals; D001835:Body Weight; D019070:Cell Lineage; D049109:Cell Proliferation; D004817:Epidermis / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000166:cytology; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013545:Sweat Glands / Q000502:physiology*
chemical_list: C489421:Bmi1 protein, mouse; C493597:Lgr5 protein, mouse; C548022:Lgr6 protein, mouse; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D063150:Polycomb Repressive Complex 1
keywords: Acral epithelium; B lymphoma Mo-MLV insertion region 1; Leucine-rich repeat-containing G protein-coupled receptor 5; Leucine-rich repeat-containing G protein-coupled receptor 6; Stem cell