Identification of stem cells by developing next generation lineage tracing methods

• Project/Area Number: 15K14531
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Developmental 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 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 幹細胞 / 発生工学 / 発生

Outline of Final Research Achievements

Stem cells are very important cells that have roles in maintaining tissue homeostasis. However, not many adult stem cells have been accurately identified. To identify adult stem cells, genetic lineage tracing method has been one of the most powerful method. However, the defect of the original method was that the it can utilize basically only one stem cell marker. However, in many cases, very specific markers have not been identified for adult stem cells. In this project, we created two systems to identify adult stem cells. One is that two-step lineage tracing method in which stem cells that coexpress two markers can be labeled, and another is super multicolor lineage tracing method in which stem cells can be labeled with 10-35 different colors. We have already made the constructs for two methodologies and we are currently generating mice.

Research Products

• [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 Issue: 1 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 Issue: 8 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 Issue: 1 Pages: 39386-39391
  • DOI: 10.1038/srep39386
  • Peer Reviewed / Open Access
• [Journal Article] Lingual Epithelial Stem Cells and Organoid Culture of Them (2016)
  • Author(s): Hisha H, Tanaka T, Ueno H
  • Journal Title: International Journal of Molecular Sciences Volume: 17 Issue: 2 Pages: 168-179
  • DOI: 10.3390/ijms17020168
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Maintenance of sweat glands by stem cells located in the acral epithelium. (2015)
  • Author(s): 1.Ohe S, Tanaka T, Yanai H, Komai Y, Omachi T, Kanno S, Tanaka K, Ishigaki K, Saiga K, Nakamura N, Ohsugi H, Tokuyama Y, Atsumi N, Hisha H, Yoshida N, Kumano K, Yamazaki F, Okamoto H, Ueno H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 466 Issue: 3 Pages: 333-338
  • DOI: 10.1016/j.bbrc.2015.09.022
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intracellular signals of lung cancer cells as possible therapeutic targets. (2015)
  • Author(s): Tanaka K, Kumano K, Ueno H
  • Journal Title: Cancer Science Volume: 未定 Issue: 5 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 / Invited
• [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] 多色細胞系譜追跡法による幹細胞・発生研究 (2016)
  • Author(s): 上野博夫
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2016-03-17
  • 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: 神戸ポートアイランド
  • Year and Date: 2015-12-04
  • Int'l Joint Research / 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: 名古屋国際会議場
  • Year and Date: 2015-10-08
  • Int'l Joint Research / 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: 名古屋国際会議場
  • Year and Date: 2015-05-01
  • Invited
• [Remarks] 関西医科大学医学部 実験病理学講座
  • URL: http://www.tnoc.kmu.ac.jp/pathol1/index.html