Elucidation of supply system of hormone-producing cells by genetic tracking of adult pituitary stem/progenitor cells

• Project/Area Number: 15K18801
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science
• Research Institution: Tottori University
• Principal Investigator: Higuchi Masashi 鳥取大学, 農学部, 講師 (70614791)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 下垂体 / 成体 / 幹・前駆細胞 / ホルモン / 発生 / 分化 / ニッチ / 転写因子 / 細胞・組織

Outline of Final Research Achievements

We searched the origin of pituitary stem/progenitor cells present only in the adult and analyzed the differentiation potential into the hormone-producing cells of anterior pituitary. Experiments using mice capable of tracking neural crest cells demonstrated that some of the stem/progenitor cells and hormone-producing cells present in the adult pituitary gland originated from the neural crest. In addition, we revealed that cell clusters isolated from rat pituitary capable of fluorescently labeling S100β expressing cells, which were not present in fetal pituitary, and cell line Tpit/F1 of candidate pituitary stem/progenitor cell possess the stemness and differentiate into hormone-producing cells. These results indicate that stem cells not originating from the oral ectoderm are present in the adult, and that these stem cells are also a source of hormone-producing cells.

Research Products

• [Journal Article] Clump formation in mouse pituitary-derived non-endocrine cell line Tpit/F1 progresses differentiation into growth hormone-producing cells (2017)
  • Author(s): Higuchi M, Yoshida S, Kanno N, Mitsuishi H, Ueharu H, Chen M, Nishimura N, Kato T, Kato Y.
  • Journal Title: Cell Tissue Res. Volume: in press Issue: 2 Pages: 353-368
  • DOI: 10.1007/s00441-017-2603-2
  • Peer Reviewed / Open Access
• [Journal Article] Gene tracing analysis reveals the contribution of neural crest-derived cells in pituitary development (2016)
  • Author(s): Ueharu H, Yoshida S, Kikkawa T, Kanno N, Higuchi M, Kato T, Osumi N, Kato Y
  • Journal Title: Journal of Anatomy Volume: 230 Issue: 3 Pages: 373-380
  • DOI: 10.1111/joa.12572
  • Peer Reviewed / Open Access
• [Journal Article] Isolation of adult pituitary stem/progenitor cell clusters located in the parenchyma of the rat anterior lobe (2016)
  • Author(s): Yoshida S, Nishimura N, Ueharu H, Kanno N, Higuchi M, Horiguchi K, Kato T, Kato Y
  • Journal Title: Stem Cell Res. Volume: 17 Issue: 2 Pages: 318-329
  • DOI: 10.1016/j.scr.2016.08.016
  • Peer Reviewed / Open Access
• [Journal Article] CXCL10/CXCR3 signaling mediates inhibitory action by Interferon-Gamma on CRF-stimulated adrenocorticotropic hormone (ACTH) release. (2016)
  • Author(s): Horiguchi K, Fujiwara K, Tsukada T, Yoshida S, Higuchi M, Tateno K, Hasegawa R, Takigami S, Ohsako S, Yashiro T, Kato T, Kato Y.
  • Journal Title: Cell Tissue Res Volume: 0 Issue: 2 Pages: 0-0
  • DOI: 10.1007/s00441-015-2317-2
  • Peer Reviewed
• [Journal Article] Search for regulatory factors of the pituitary-specific transcription factor PROP1 gene (2016)
  • Author(s): Nishimura N, Ueharu H, Nishihara H, Shibuya S, Yoshida S, Higuchi M, Kanno N, Horiguchi K, Kato T, Kato Y
  • Journal Title: Journal of Reproduction and Development Volume: 62 Issue: 1 Pages: 93-102
  • DOI: 10.1262/jrd.2015-092
  • NAID: 130005126320
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] Expression studies of Neuronatin in the prenatal and postnatal rat pituitary. (2015)
  • Author(s): Kanno N, Higuchi M, Yoshida S, Yako H, Chen M, Ueharu H, Nishimura N, Mitsuishi H, Kato T, Kato Y.
  • Journal Title: Cell Tissue Res Volume: 0 Issue: 2 Pages: 0-0
  • DOI: 10.1007/s00441-015-2325-2
  • Peer Reviewed
• [Presentation] Neuronatin emerges in the rat pituitary stem/progenitor cells and terminates its role in the terminally differentiating cells (2015)
  • Author(s): Kanno N, Higuchi M, Yoshida S, Yako H, Chen M, Ueharu H, Nishimura N, Nishihara H, Kato T, Kato Y
  • Organizer: Society for Endocrinology BES 2015
  • Place of Presentation: Edinburgh International Conference Centre (Edinburgh, UK)
  • Year and Date: 2015-11-02
  • Int'l Joint Research
• [Presentation] ラット下垂体ならびに生殖器におけるNeuronatinの局在解析 (2015)
  • Author(s): 菅野尚子, 樋口雅司, 吉田彩舟, 八子英司, 陳黙, 上春浩貴, 西村直人, 西原大翔, 加藤たか子, 加藤幸雄
  • Organizer: 第108回日本繁殖生物学会大会
  • Place of Presentation: 宮崎大学（宮崎県宮崎市）
  • Year and Date: 2015-09-17
• [Presentation] 成体下垂体幹細胞におけるAQP5の発現と運動性繊毛の形成 (2015)
  • Author(s): 樋口雅司, 菅野尚子, 加藤たか子, 加藤幸雄
  • Organizer: 日本畜産学会第120回大会
  • Place of Presentation: 酪農学園大学（北海道江別市）
  • Year and Date: 2015-09-11
• [Presentation] NeuronatinはCa2+濃度を調節する細胞内小器官に局在し下垂体の分化に寄与する (2015)
  • Author(s): 菅野尚子, 樋口雅司, 吉田彩舟, 八子英司, 陳黙, 上春浩貴, 西村直人, 西原大翔, 加藤たか子, 加藤幸雄
  • Organizer: 日本下垂体研究会第30回学術集会
  • Place of Presentation: 黒部市宇奈月国際会館セレネ・ホテル黒部（富山県黒部市）
  • Year and Date: 2015-08-05