Stemness and tumorigenesis of salivary gland myoepithelial cells

• Project/Area Number: 15H05013
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Showa University
• Principal Investigator: Mishima Kenji 昭和大学, 歯学部, 教授 (50275343)
• Co-Investigator(Kenkyū-buntansha): 入江 太朗 岩手医科大学, 歯学部, 教授 (00317570) ; 安原 理佳 昭和大学, 歯学部, 講師 (20453649) ; 田中 準一 昭和大学, 歯学部, 助教 (40710166) ; 馬渕 洋 東京医科歯科大学, 大学院保健衛生学研究科, 助教 (50424172) ; 斎藤 一郎 鶴見大学, 歯学部, 教授 (60147634) ; 桐田 忠昭 奈良県立医科大学, 医学部, 教授 (70201465) ; 阪井 丘芳 大阪大学, 歯学研究科, 教授 (90379082) ; 福島 美和子 昭和大学, 歯学部, 助教 (90548273) ; 河野 葉子 昭和大学, 歯学部, 准教授 (40195681)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
• Keywords: 唾液腺 / 再生 / 筋上皮細胞 / 幹細胞 / 再生医療 / 多分化能 / 腫瘍原性

Outline of Final Research Achievements

We attempted to identify stem/progenitor cells in salivary gland. Localization of BrdU label-retaining cells were found specifically in myoepthelial cells located between luminal and stroma cells after 30 weeks, suggesting that myoepithelial cells were expected to be one of putative stem cells. The data from RNA-seq showed CD49fhigh subset contained positive cells for both of αSMA and Myh11, a marker of myoepithelial cells, demonstrating that CD49fhigh subset consisted of myoepithelial cell-enriched population. The selection of a CD49fhigh subset showed high ability of sphere formation and was differentiated into ductal lineage in vitro. These data suggest that the enriched myoepithelial cell compartment may contain stem/progenitor cells in salivary glands since the cells enriched in CD49fhigh subset showed multipotent properties by sphere formation.

Research Products

• [Journal Article] The Role of the Slc39a Family of Zinc Transporters in Zinc Homeostasis in Skin (2018)
  • Author(s): Bin Bum-Ho、Hojyo Shintaro、Seo Juyeon、Hara Takafumi、Takagishi Teruhisa、Mishima Kenji、Fukada Toshiyuki
  • Journal Title: Nutrients Volume: 10 Issue: 2 Pages: 219-219
  • DOI: 10.3390/nu10020219
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of mouse gingival junctional epithelial cell line using a bioengineered tooth (2018)
  • Author(s): Seki T, Aizawa R, Tanaka J, Yajima-Himuroa S, Kato M, Tanaka K, Mishima K, Yamamoto M.
  • Journal Title: Biochem Biophys Res Commun Volume: 047 Issue: 1 Pages: 167-172
  • DOI: 10.1016/j.bbrc.2018.02.047
  • Peer Reviewed / Open Access
• [Journal Article] Requirement of zinc transporter ZIP10 for epidermal development: Implication of the ZIP10-p63 axis in epithelial homeostasis. (2017)
  • Author(s): 1.Bin BH , Bhin J , Takaishia M , Toyoshima K , Kawamata S , Ito K , Hara T , Watanabe T , Irie T , Takagishi T, Lee SH , Jung HS, Rho S , Seo J , Choi DH, Hwang D , Koseki H , Ohara O , Sano S , Tsuji T , Mishima K , Fukada T.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114 Issue: 46 Pages: 12243-12246
  • DOI: 10.1073/pnas.1710726114
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage (2017)
  • Author(s): Hoshino Marie、Kaneko Kotaro、Miyamoto Yoichi、Yoshimura Kentaro、Suzuki Dai、Akaike Takaaki、Sawa Tomohiro、Ida Tomoaki、Fujii Shigemoto、Ihara Hideshi、Tanaka Junichi、Tsukuura Risa、Chikazu Daichi、Mishima Kenji、Baba Kazuyoshi、Kamijo Ryutaro
  • Journal Title: Free Radic Biol Med Volume: 110 Pages: 63-71
  • DOI: 10.1016/j.freeradbiomed.2017.05.022
  • Peer Reviewed / Open Access
• [Journal Article] Resveratrol improves salivary dysfunction in a non-obese diabetic (NOD) mouse model of Sjögren’s syndrome (2016)
  • Author(s): Inoue H, Kishimoto A, Nakayama RU, Hasaka A, Takahashi A, Ryo A, Muramatsu T, Ide F, Mishima K, Saito I
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 59 Issue: 2 Pages: 107-112
  • DOI: 10.3164/jcbn.16-31
  • NAID: 130005262395
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Presentation] MOUSE SALIVARY GLAND-DERIVED MYOEPITHELIAL CELLS SHOWS STEM/PROGENITOR CELL PROPERTIES IN VITRO (2017)
  • Author(s): Rika Yasuhara, Junichi Tanaka, Miwako Fukushima, Tarou Irie, Kenji Mishima
  • Organizer: 国際幹細胞学会
  • Int'l Joint Research
• [Presentation] 唾液腺由来筋上皮細胞の単離と性質解析 (2016)
  • Author(s): 安原理佳、田中準一、福島美和子、入江太朗、河野葉子、美島健二
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] 唾液腺由来筋上皮細胞の単離と性質解析 (2016)
  • Author(s): Yasuhara R, Tanaka J, Fukushima M, IrieT , Kohno Y, Mishima K
  • Organizer: 105回日本病理学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-05-12
• [Presentation] 唾液腺由来筋上皮細胞の性質解析 (2015)
  • Author(s): 安原 理佳, 田中 準一, 福島 美和子, 入江 太朗, 河野 葉子, 美島 健二
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01