Toward understanding regulatory mechanisms of stem cell homeostasis in hair follicle

• Project/Area Number: 15K19709
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Morita Ritsuko 国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 研究員 (20700040)
• 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: live imaging / single cell RNA-seq / Live imaging / Single cell RNA-seq / 毛包幹細胞

Outline of Final Research Achievements

In this study, we investigated the induction mechanisms of mouse hair follicle stem cells and their surrounding microenvironment by combining two marker-independent single cell methods, namely the single-cell resolution 4D live imaging and single-cell transcriptome. We established an ex vivo live imaging system for developing hair follicles that can visualize the cell behaviour and lineages of every cell at single cell resolution. Retrospective tracking of the stem and differentiated cells in time-lapse image data revealed the originating region of the hair follicle stem cells and their developmental dynamics and lineages. Moreover, we obtained single-cell transcriptome data from embryonic hair follicle throughout development and transcriptome analysis revealed the changes of cellular status leading to the emergence of stem cell population during hair follicle development.

Academic Significance and Societal Importance of the Research Achievements

本研究により、一見均質な細胞から幹細胞と分化細胞が生み出され組織の秩序や恒常性が形成されていく仕組みを理解することは、毛包だけでなく多くの器官発生に普遍的に存在する「可塑性と頑強性」の理解に繋がると期待される。さらに、幹細胞の適切な維持・制御に必須な細胞周辺環境の解明につながれば、生体外における毛包培養や胎仔性幹細胞の誘導・増殖・分化の制御技術の開発に大きく寄与することが期待され、将来的には薬剤評価系の確立など、皮膚や毛包に伴うがんや疾病に向けた創薬開発に貢献できると期待される。

Research Products

• [Journal Article] Coordination of cellular dynamics contributes to tooth epithelium deformations. (2016)
  • Author(s): Morita, R., Kihara, M., Nakatsu, Y., Nomoto, Y., Ogawa, M., Ohashi, K., Mizuno, K., Tachikawa, T., Ishimoto, Y., Morishita, Y., and Tsuji, T.
  • Journal Title: PLoS One Volume: 11 Issue: 9 Pages: 1-20
  • DOI: 10.1371/journal.pone.0161336
  • Peer Reviewed / Open Access
• [Journal Article] Tooth germ invagination from cell-cell interaction: Working hypothesis on the mechanical instability (2015)
  • Author(s): Hisako Takigawa-Imamura, Ritsuko Morita, Takafumi Iwaki, Takashi Tsuji and Kenichi Yoshikawa
  • Journal Title: Journal of Theoretical Biology Volume: 382 Pages: 284-291
  • DOI: 10.1016/j.jtbi.2015.07.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 毛包幹細胞の起源と誘導メカニズムの解明を目指して (2017)
  • Author(s): 森田梨津子
  • Organizer: 第５回「皮膚の会」
  • Place of Presentation: I ＆ I LAND アイ・アイ・ランド (大阪府四條畷市)
  • Year and Date: 2017-03-04
• [Presentation] Deciphering the molecular and cellular basis of the induction of hair follicle stem cells at single cell resolution (2017)
  • Author(s): Ritsuko Morita, Noriko Sanzen, Tetsutaro Hayashi, Mana Umeda, Mika Yoshimura, Itoshi Nikaido, Takaya Abe, Hiroshi Kiyonari, Yasuhide Furuta and Hironobu Fujiwara
  • Organizer: RIKEN Joint Retreat 2017
  • Place of Presentation: Hamanako Royal Hotel (Shizuoka, Hamamatsu)
  • Year and Date: 2017-02-02
• [Presentation] Deciphering the molecular and cellular basis of the induction of hair follicle stem cells at single cell resolution (2016)
  • Author(s): Ritsuko Morita, Noriko Sanzen, Tetsutaro Hayashi, Mana Umeda, Mika Yoshimura, Itoshi Nikaido, Takaya Abe, Hiroshi Kiyonari, Yasuhide Furuta and Hironobu Fujiwara
  • Organizer: The 27th CDB Meeting "Body surface tactics: cellular crosstalk for the generation of super-biointerfaces"
  • Place of Presentation: RIKEN CDB (Hyogo, Kobe)
  • Year and Date: 2016-11-14
  • Int'l Joint Research