The effects of environmental factors on hair follicle stem cell

• Project/Area Number: 17K15663
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Experimental pathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Morinaga Hironobu 東京医科歯科大学, 難治疾患研究所, プロジェクト助教 (70707942)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 毛包幹細胞 / 肥満 / 皮膚 / 環境要因 / 分化

Outline of Final Research Achievements

By using mouse skin as a model, I investigated how environmental factors, especially obesity, affect the maintenance of skin homeostasis. It was known that the number of hair follicles in mice decreases with age, as in humans. Here I showed that hair loss is accelerated in an obese mice. The direct cause of hair loss is the conversion of hair follicle stem cells to epidermal keratinocytes. As for changes in internal factors, obesity causes activation of IL1R signaling and lipid accumulation in hair follicle stem cells, which in turn leads to inactivation of SHH signaling, which is essential for the maintenance of hair follicle stem cells. This study has revealed the entire process of hair loss from the systemic changes of obesity.

Translated with www.DeepL.com/Translator (free version)

Academic Significance and Societal Importance of the Research Achievements

組織や臓器は加齢によってその機能が低下し、最終的には個体の死に繋がる。加齢による組織の機能低下は避けられないものであるが、その仕組みの理解は治療や新規薬剤の可能性を生み出し、健康寿命の延伸へとつながることが期待される。昨今特に先進国で深刻な問題となっている肥満は、特定の臓器でがんを誘発するなど様々な疾患のリスクファクターとなることが知られている。本研究では毛包を組織のモデルとし、肥満がいかに毛包の維持に有害か、その詳細な因子・メカニズムについて明らかにした。本研究は環境因子が組織の恒常性維持に与える影響を明らかにするとともに、脱毛予防や治療に対する新たな戦略を創造した。

Research Products

• [Journal Article] Obesity accelerates hair thinning by stem cell-centric converging mechanisms (2021)
  • Author(s): Morinaga H, Mohri Y, Grachtchouk M, Asakawa K, Matsumura H, Oshima M, Takayama N, Kato T, Nishimori Y, Sorimachi Y, Takubo K, Suganami T, Iwama A, Iwakura Y, Dlugosz AA & Nishimura EK
  • Journal Title: Nature Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stem cell competition orchestrates skin homeostasis and ageing (2019)
  • Author(s): Liu N, Matsumura H, Kato T, Ichinose S, Takada A, Namiki T, Asakawa K, Morinaga H, Mohri Y, De Arcangelis A, Geroges-Labouesse E, Nanba D, Nishimura EK
  • Journal Title: Nature Volume: 568(7752) Issue: 7752 Pages: 344-350
  • DOI: 10.1038/s41586-019-1085-7
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] iNOS inhibits hair regeneration in obese diabetic (ob/ob) mice (2018)
  • Author(s): Sasaki M, Shinozaki S, Morinaga H, Kaneki M, Nishimura EK, Shimokado K
  • Journal Title: Biochem Biophys Res Commun. Volume: 印刷中 Issue: 4 Pages: 893-897
  • DOI: 10.1016/j.bbrc.2018.05.071
  • Peer Reviewed