Identification of cells that control gonadal sex stability

• Project/Area Number: 17K19375
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biology of Cells to Organisms, and related fields
• Research Institution: Tokyo Medical and Dental University (2018); Akita University (2017)
• Principal Investigator: Sasaki Junko 東京医科歯科大学, 難治疾患研究所, 准教授 (30333371)
• Research Collaborator: KANAI yoshiakira
• Project Period (FY): 2017-06-30 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: 性分化 / 細胞内シグナル伝達 / シグナル伝達 / 細胞・組織 / 脂質

Outline of Final Research Achievements

We made the conditional knockout mice lacking the phospholipid metabolizing enzymes (ITG-cre LKO mice) and found that in ITG-cre LKO XX gonads, Sertoli-like cells begin to appear at about 2 weeks of age. By ovarian transplantation and validation of Cre gene expression using Cre-reporter mice, we revealed that the cells emerged in granulosa layer transiently can regulate female gonadal sex stability through phospholipid metabolism.

Academic Significance and Societal Importance of the Research Achievements

本研究により見出した卵巣顆粒膜層に一過的に存在する細胞およびその細胞におけるリン脂質代謝が卵巣の性を制御するという知見は、学術的に新規の知見である。また、ITG-cre LKO雌マウスは不妊であることから、本研究の成果は早発卵巣不全の病因という医学的に重要な知見を提供することが期待される。

Research Products

• [Journal Article] A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection (2019)
  • Author(s): Fujioka Y, Satoh AO, Horiuchi K, Fujioka M, Tsutsumi K, Sasaki J, Nepal P, Kashiwagi S, Paudel S, Nishide S, Nanbo A, Sasaki T, Ohba Y
  • Journal Title: Cell Structure and Function Volume: 44 Issue: 1 Pages: 61-74
  • DOI: 10.1247/csf.19001
  • NAID: 130007636814
  • ISSN: 0386-7196, 1347-3700
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lysophosphatidylinositol‐acyltransferase‐1 is involved in cytosolic Ca2+ oscillations in macrophages (2019)
  • Author(s): Takemasu Shinya、Ito Masaki、Morioka Shin、Nigorikawa Kiyomi、Kofuji Satoshi、Takasuga Shunsuke、Eguchi Satoshi、Nakanishi Hiroki、Matsuoka Isao、Sasaki Junko、Sasaki Takehiko、Hazeki Kaoru
  • Journal Title: Genes to Cells Volume: - Issue: 5 Pages: 1-11
  • DOI: 10.1111/gtc.12681
  • Peer Reviewed / Open Access
• [Journal Article] PIKfyve regulates melanosome biogenesis (2018)
  • Author(s): Liggins Marc C.、Flesher Jessica L.、Jahid Sohail、Vasudeva Priya、Eby Victoria、Takasuga Shunsuke、Sasaki Junko、Sasaki Takehiko、Boissy Raymond E.、Ganesan Anand K.
  • Journal Title: PLOS Genetics Volume: 14 Issue: 3 Pages: e1007290-e1007290
  • DOI: 10.1371/journal.pgen.1007290
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PTEN Regulates PI(3,4)P 2 Signaling Downstream of Class I PI3K (2017)
  • Author(s): Malek M、Kielkowska A、Chessa T、Anderson K E.、Barneda D、Pir P、Nakanishi H、Eguchi S、Koizumi A、Sasaki J、Juvin V、Kiselev VY.、Niewczas I、Gray A、Valayer A、Spensberger D、Imbert M、Felisbino S、Habuchi T、Beinke S、Cosulich S、Le Novere N、Sasaki T、Clark J、Hawkins PT.、Stephens LR.
  • Journal Title: Molecular Cell Volume: 68 Issue: 3 Pages: 566-580
  • DOI: 10.1016/j.molcel.2017.09.024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The effect and possible clinical efficacy of in vivo inhibition of neutrophil extracellular traps by blockade of PI3K-gamma on the pathogenesis of microscopic polyangiitis (2017)
  • Author(s): Kimura Hirotaka、Matsuyama Yasushi、Araki Sachiko、Koizumi Atsushi、Kariya Yumi、Takasuga Shunsuke、Eguchi Satoshi、Nakanishi Hiroki、Sasaki Junko、Sasaki Takehiko
  • Journal Title: Modern Rheumatology Volume: 28 Issue: 3 Pages: 530-541
  • DOI: 10.1080/14397595.2017.1367116
  • Peer Reviewed / Open Access
• [Journal Article] Docosahexaenoic acid preserves visual function by maintaining correct disc morphology in retinal photoreceptor cells (2017)
  • Author(s): Shindou Hideo、Koso Hideto、Sasaki Junko、Nakanishi Hiroki、Sagara Hiroshi、Nakagawa Koh M.、Takahashi Yoshikazu、Hishikawa Daisuke、Iizuka-Hishikawa Yoshiko、Tokumasu Fuyuki、Noguchi Hiroshi、Watanabe Sumiko、Sasaki Takehiko、Shimizu Takao
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 29 Pages: 12054-12064
  • DOI: 10.1074/jbc.m117.790568
  • Peer Reviewed / Open Access
• [Journal Article] Lysophosphatidic acid acyltransferase 3 tunes the membrane status of germ cells by incorporating docosahexaenoic acid during spermatogenesis (2017)
  • Author(s): Iizuka-Hishikawa Yoshiko、Hishikawa Daisuke、Sasaki Junko、Takubo Keiyo、Goto Motohito、Nagata Katsuyuki、Nakanishi Hiroki、Shindou Hideo、Okamura Tadashi、Ito Chizuru、Toshimori Kiyotaka、Sasaki Takehiko、Shimizu Takao
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 29 Pages: 12065-12076
  • DOI: 10.1074/jbc.m117.791277
  • Peer Reviewed / Open Access
• [Presentation] Molecular mechanisms of phosphoinositide signaling (2019)
  • Author(s): Junko Sasaki
  • Organizer: 9th FAOPS Congress
  • Int'l Joint Research
• [Presentation] INPP4B is a tumor suppressor in the context of PTEN insufficiency by modulating the levels of PI3K lipid products (2017)
  • Author(s): Takehiko Sasaki,Hiroki Nakanishi,Satoshi Eguchi,and Junko Sasaki
  • Organizer: International Symposium on Imaging Frontier 2017
  • Int'l Joint Research
• [Presentation] イノシトールリン脂質クオリティとシグナル伝達 (2017)
  • Author(s): 佐々木純子、中西広樹、刈屋佑美、江口賢史、佐々木雄彦
  • Organizer: 第69回日本細胞生物学会大会
• [Presentation] 性転換とリン脂質代謝 (2017)
  • Author(s): 佐々木純子
  • Organizer: リポクオリティ領域若手研究発表会
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bisei/