Identification of lingual and esophageal epithelial stem cells and their hierarchy, and of target genes for cancer treatment

• Project/Area Number: 15H02364
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kansai Medical University
• Principal Investigator: UENO Hiroo 関西医科大学, 医学部, 教授 (60332368)
• Co-Investigator(Kenkyū-buntansha): 厚海 奈穂 関西医科大学, 医学部, 助教 (90612151)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥42,900,000 (Direct Cost: ¥33,000,000、Indirect Cost: ¥9,900,000); Fiscal Year 2017: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000); Fiscal Year 2016: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000); Fiscal Year 2015: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• Keywords: 幹細胞 / 癌 / 発生、分化

Outline of Final Research Achievements

It has been proposed by Doupe et al (2012 Science) that the specific adult stem cells do not exist in the esophageal epithelial tissue. We by the multicolor cell lineage tracing method found that the gene A positive esophageal epithelial basal cells include esophageal epithelial stem cells. Also, by single cell RNAseq method of isolated esophageal epithelial tissue, and cell clustering based on the expressed genes, we identified a group of esophageal epithelial stem cells, and specific markers for them. In particular, one of them, gene B was found to be an useful esophageal epithelial stem cell marker. We also identified genes C positive taste bud cells in the tongue epithelial tissues are taste bud stem cells.

Research Products

• [Journal Article] Tumor-targeting Salmonella typhimurium A1-R inhibited osteosarcoma angiogenesis in the in vivo Gelfoam R assay visualized by color-coded imaging. (2018)
  • Author(s): Asano T., et al.
  • Journal Title: Anticancer Volume: 420 Pages: 100-106
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Intestinal cancer stem cells marked by Bmi1 or Lgr5 expression contribute to tumor propagation via clonal expansion (2017)
  • Author(s): Hirotsugu Yanai, Naho Atsumi, Toshihiro Tanaka, Naohiro Nakamura, Yoshihiro Komai, Taichi Omachi, Kiyomichi Tanaka, Kazuhiko Ishigaki, Kazuho Saiga, Haruyuki Ohsugi, Yoko Tokuyama, Yuki Imahashi, Shuichi Ohe, Hiroko Hisha, Naoko Yoshida, Keiki Kumano, Masanori Kon and Ueno H.
  • Journal Title: Scientific Reports Volume: 7 Pages: 41838-41847
  • DOI: 10.1038/srep41838
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of mouse cochlear progenitors that develop hair and supporting cells in the organ of Corti. (2017)
  • Author(s): Jinshu Xu, H Ueno ,Chelsea Xu, Binglai Chen, Irving Weissman, and Pin-Xian Xu
  • Journal Title: Nature Communications Volume: -
  • Int'l Joint Research
• [Journal Article] Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem cell self-renewal (2017)
  • Author(s): KS Yan, CY Janda, J Chang, GXY Zheng, KA Larkin, VC Luca, LA Chia, AT Mah, A Han, JM Terry, A Ootani, K Roelf, M Lee, J Yuan, X Li, CR Bolen,J Wilhelmy, PS Davies, H Ueno , RJ von Furstenberg, P Belgrader, SB Ziraldo, H Ordonez, SJ Henning, MH Wong, MP Snyder, IL Weissman, AJ Hsueh, TS Mikkelsen, KC Garcia, and CJ Kuo
  • Journal Title: Nature Volume: -
  • Int'l Joint Research
• [Journal Article] Identification of normal and neoplastic stem cells by the multicolor lineage tracing method. (2016)
  • Author(s): Ueno H
  • Journal Title: Pathology International Volume: 66 Pages: 423-430
  • DOI: 10.1111/pin.12425
  • Peer Reviewed
• [Journal Article] Bmi1-positive cells in the lingual epithelium could serve as cancer stem cells in tongue cancer. (2016)
  • Author(s): T Tanaka, N Atsumi, N Nakamura, H Yanai, Y Komai, T Omachi, K Tanaka, K Ishigaki, K Saiga, H Ohsugi, Y Tokuyama, Y Imahashi, H Hisha, N Yoshida, K Kumano, K Okazaki, and Ueno H
  • Journal Title: Scientific Reports Volume: 6 Pages: 39386-39391
  • DOI: 10.1038/srep39386
  • Peer Reviewed / Open Access
• [Journal Article] Intracellular signals of lung cancer cells as possible therapeutic targets (2015)
  • Author(s): Tanaka K, Kumano K, Ueno H
  • Journal Title: Cancer Sci. Volume: 未定 Pages: 489-496
  • DOI: 10.1111/cas.12643
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] organoids of tongue and esophagus (2016)
  • Author(s): 上野博夫
  • Organizer: EMBO|EMBL Symposium
  • Place of Presentation: ドイツ ハイデルベルク
  • Year and Date: 2016-10-12
  • Int'l Joint Research
• [Presentation] 多色細胞系譜追跡法による新規成体幹細胞、がん幹細胞の同定 (2016)
  • Author(s): 上野博夫
  • Organizer: 第25回日本形成外科学会基礎学術集会
  • Place of Presentation: 大阪 ナレッジキャピタル コングレ・コンベンションセンター
  • Year and Date: 2016-09-15
  • Invited
• [Presentation] Identification of novel stem cells by the multicolor lineage tracing method (2015)
  • Author(s): 上野博夫
  • Organizer: BMB2015(第38回日本分子生物学会年会 第88回日本生化学大会 合同大会)
  • Place of Presentation: 神戸 神戸ポートアイランド
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] Indentification of normal and cancer stem cells and their niche (2015)
  • Author(s): 上野博夫
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] 多色細胞系譜追跡法による成体幹細胞・がん幹細胞の解析 (2015)
  • Author(s): 上野博夫
  • Organizer: 平成27年度「がん研究分野の特性等を踏まえた支援活動」支援説明会・公開シンポジウム
  • Place of Presentation: 東京 一橋講堂 学術総合センター
  • Year and Date: 2015-09-09
  • Invited
• [Presentation] 多色細胞系譜追跡による成体幹細胞の同定・発生・がん化研究 (2015)
  • Author(s): 上野博夫
  • Organizer: 関西眼科先進医療研究会
  • Place of Presentation: 大阪 大阪大学
  • Year and Date: 2015-07-01
  • Invited
• [Presentation] 新規成体幹細胞の同定とがん化における細胞動態解析 (2015)
  • Author(s): 上野博夫
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋 名古屋国際会議場
  • Year and Date: 2015-04-30
  • Invited
• [Remarks] 関西医科大学実験病理学講座
  • URL: http://www3.kmu.ac.jp/pathol1/index.html