Studies of the roles of pituitary stem/progenitor cells that express the transcription factors, PROP1 and PRXs

• Project/Area Number: 15K07771
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: Meiji University
• Principal Investigator: Kato Takako 明治大学, 研究・知財戦略機構, 研究推進員 (90445859)
• Co-Investigator(Renkei-kenkyūsha): KATO YUKIO 明治大学, 農学部, 教授 (30114177)
• Project Period (FY): 2015-10-21 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 下垂体 / 幹細胞 / 生殖 / 分化 / 組織形成 / 転写因子 / 神経堤 / 血管形成 / 遺伝子 / 発現制御 / 内分泌学 / 細胞・組織 / 内分泌

Outline of Final Research Achievements

The pituitary gland is an endocrine organ that locates beneath the brain and synthesizes hormones important for maintenance of vital functions. The development and differentiation of tissues is progressing through the spatiotemporal expression of many transcription factors. This project focuses on the role of the pituitary-specific transcription factor, PROP1, and a novel pituitary transcription factor, PRX2 involved in pituitary organogenesis. Our studies have demonstrated following important results: 1) the responsive regions of many factors are present in the upstream promoter of PROP1 gene, 2) methylation of this gene is partially involved in expression in early development, 3) retinoid regulates the expression of PROP1 in the pituitary primordium, 4) PRX1- and PRX2-positive cells in the pituitary mesenchyme are involved in the pituitary vasculogenesis, 5) TtT / GF cells, expressing PRXs, derived from pituitary tumors, change into cells that express pericyte-like genes by TGFβ.

Research Products

• [Journal Article] Retinoic acid signalling is a candidate regulator of the expression of pituitary-specific transcription factor Prop1 in the developing rodent pituitary (2018)
  • Author(s): Yoshida S.、Fujiwara K.、Nishihara H.、Kato T.、Yashiro T.、Kato Y.
  • Journal Title: Journal of Neuroendocrinology Volume: 30 Issue: 3
  • DOI: 10.1111/jne.12570
  • Peer Reviewed / Open Access
• [Journal Article] Cell type-specific localization of Ephs pairing with ephrin-B2 in the rat postnatal pituitary gland. (2017)
  • Author(s): Yoshida S, Kato T, Kanno N, Nishimura N, Nishihara H, Horiguchi K, Kato Y.
  • Journal Title: Cell Tissue Res. Volume: 370 Issue: 1 Pages: 99-112
  • DOI: 10.1007/s00441-017-2646-4
  • Peer Reviewed
• [Journal Article] SOX10-positive cells emerge in the rat pituitary gland during late embryogenesis and start to express S100B (2017)
  • Author(s): H. Ueharu, S. Yoshida, N. Kanno, K. Horiguchi, N. Nishimura, T. Kato, Y. Kato
  • Journal Title: Cell and Tissue Res. Volume: 372 Issue: 1 Pages: 77-90
  • DOI: 10.1007/s00441-017-2724-7
  • Peer Reviewed
• [Journal Article] TGFbeta signaling reinforces pericyte properties of the non-endocrine mouse pituitary cell line TtT/GF (2017)
  • Author(s): Tsukada, T., Yoshida, S., Kito, K., Fujiwara, K., Yako, H., Horiguchi, K., Isowa, Y., Yashiro, T., Kato, T., and Kato, Y
  • Journal Title: Cell Tissue Res Volume: 371 Pages: 339-350
  • Peer Reviewed
• [Journal Article] Construction and expression of vectors encoding biologically active rodent gonadotropins (2017)
  • Author(s): A. Ohta, Y. Tsunoda, Y. Tamura, K. Iino, N. Nishimura, H. Nishihara, H. Takanashi, S. Yoshida, T. Kato, Y. Kato.
  • Journal Title: Journal of Reproduction and Development Volume: 63 Issue: 6 Pages: 605-609
  • DOI: 10.1262/jrd.2017-091
  • NAID: 130006250258
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [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] Involvement of DNA methylation in regulating rat <i>Prop1</i> gene expression during pituitary organogenesis (2017)
  • Author(s): Nishihara H, Yoshida S, Kanno N, Nishimura N, Ueharu H, Ohgane J, Kato T, Kato Y
  • Journal Title: Journal of Reproduction and Development Volume: 63 Issue: 1 Pages: 37-44
  • DOI: 10.1262/jrd.2016-102
  • NAID: 130005332293
  • ISSN: 0916-8818, 1348-4400
  • 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] Identification of THY1 as a novel thyrotrope marker and THY1 antibody-mediated thyrotrope isolation in the rat anterior pituitary gland (2016)
  • Author(s): Horiguchi K, Nakakura T, Yoshida S, Tsukada T, Kanno N, Hasegawa R, Takigami S, Ohsako S, Kato T, Kato Y
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 480 Issue: 2 Pages: 273-279
  • DOI: 10.1016/j.bbrc.2016.10.049
  • Peer Reviewed / Open Access
• [Journal Article] S100β-positive Cells of Mesenchymal Origin Reside in the Anterior Lobe of the Embryonic Pituitary Gland (2016)
  • Author(s): Horiguchi K, Yako H, Yoshida S, Fujiwara K, Tsukada T, Kanno N, Ueharu H, Nishihara H, Kato T, Yashiro T, Kato Y
  • Journal Title: PLoS ONE Volume: 11 Issue: 10 Pages: 1-18
  • DOI: 10.1371/journal.pone.0163981
  • Peer Reviewed / Open Access
• [Journal Article] Long-chain unsaturated fatty acids reduce the transcriptional activity of the rat follicle-stimulating hormone β-subunit gene (2016)
  • Author(s): Moriyama R, Yamazaki T, Kato T, Kato Y
  • Journal Title: Journal of Reproduction and Development Volume: 62 Issue: 2 Pages: 195-199
  • DOI: 10.1262/jrd.2015-138
  • NAID: 130005146470
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [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] Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary (2016)
  • Author(s): Yoshida S, Kato T, Kato Y
  • Journal Title: Int. J. Mol. Sci. Volume: 17 Issue: 1 Pages: 75-75
  • DOI: 10.3390/ijms17010075
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] EMT Involved in Migration of Stem/Progenitor Cells for Pituitary Development and Regeneration (2016)
  • Author(s): Yoshida S, Kato T, Kato Y
  • Journal Title: J. Clin. Med. Volume: 5 Issue: 4 Pages: 43-43
  • DOI: 10.3390/jcm5040043
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transcription of follicle-stimulating hormone subunit genes is modulated by porcine LIM homeobox transcription factors, LHX2 and LHX3 (2016)
  • Author(s): Yoshida S, Kato T, Nishimura N, Kanno N, Chen M, Ueharu H, Nishihara H, Kato Y.
  • Journal Title: Journal of Reproduction and Development Volume: 62 Issue: 3 Pages: 241-248
  • DOI: 10.1262/jrd.2015-163
  • NAID: 130005157181
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [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] 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] Long-Chain Unsaturated Fatty Acids Reduce the Transcriptional Activity of the Rat Follicle-Stimulating Hormone β-Subunit Gene. (2016)
  • Author(s): Moriyama R, Yamazaki T, Kato T, Kato Y.
  • Journal Title: J Reprod Dev Volume: 0 Pages: 0-0
  • NAID: 130005146470
  • Peer Reviewed
• [Journal Article] Search for Regulatory Factors of Pituitary-specific Transcription Factor PROP1 Gene. (2016)
  • Author(s): Nishimura N, Ueharu H, Shibuya S, Nishihara H, Yoshida S, Higuchi M, Kanno N, Horiguchi K, Kato T, Kato Y.
  • Journal Title: J Reprod Dev Volume: 62 Pages: 93-102
  • NAID: 130005126320
  • Peer Reviewed
• [Journal Article] Regulatory system for stem/progenitor cell niches in the adult rodent pituitary. (2016)
  • Author(s): Yoshida S, Kato T, Kato Y.
  • Journal Title: Int J Mol Sci Volume: 0
  • Peer Reviewed
• [Journal Article] Expression of Slug in S100β protein-positive cells of the postnatal developing rat anterior pituitary gland. (2015)
  • Author(s): Horiguchi K, Fujiwara K, Tsukada T, Yako H, Tateno K, Hasegawa R, Takegami S, Osako S, Yashiro T, Kato T, Kato Y.
  • Journal Title: Cell Tissue Res Volume: 0 Issue: 2 Pages: 0-0
  • DOI: 10.1007/s00441-015-2256-y
  • Peer Reviewed
• [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
• [Journal Article] PRRX1- and PRRX2-positive mesenchymal stem/progenitor cells are involved in vasculogenesis during rat embryonic pituitary development. (2015)
  • Author(s): Higuchi M, Yoshida S, Ueharu H, Chen M, Kato T, Kato Y.
  • Journal Title: Cell Tissue Res Volume: 361 Pages: 557-565
  • Peer Reviewed
• [Journal Article] Localization of a juxtacrine factor ephrin-B2 in the pituitary stem/progenitor cell niches throughout life. (2015)
  • Author(s): Yoshida S, Kato T, Chen M, Higuchi M, Ueharu H, Nishimura N, Kato Y.
  • Journal Title: Cell Tissue Res Volume: 359 Pages: 755-766
  • Peer Reviewed
• [Presentation] 下垂体前葉内濾胞星状細胞が発現するCD抗原の探索 (2017)
  • Author(s): 堀口幸太郎, 吉田彩舟, 藤原研, 塚田岳大, 加藤たか子, 長谷川瑠美, 瀧上周, 大迫俊二, 屋代隆, 加藤幸雄
  • Organizer: 第122回日本解剖学会総会・全国学術集会
  • Place of Presentation: 長崎大学坂本キャンパス
  • Year and Date: 2017-03-28
• [Presentation] 単離した下垂体幹細胞ニッチを用いた分化誘導と制御因子の探索 (2017)
  • Author(s): 吉田彩舟, 百合野秀明, 小林正明, 菅野尚子, 上春浩貴, 矢野健太郎, 橋本真一, 加藤たか子, 加藤幸雄
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2017-03-07
• [Presentation] TGFbは下垂体由来株化細胞TtT/GFをペリサイトに誘導する (2017)
  • Author(s): 塚田岳大, 吉田彩舟, 紀藤圭治, 藤原研, 八子英司, 堀口幸太郎, 屋代隆, 加藤たか子, 加藤幸雄
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2017-03-07
• [Presentation] Analysis of the differentiation capacity of adult stem/progenitor cells in the parenchymal-niche of the rodent pituitary gland (2017)
  • Author(s): Yoshida, S., Yurino, H., Kobayashi, M., Nishimura, N., Kanno, N., Yano, K., Hashimoto, S-i., Kato, T., Kato, Y
  • Organizer: The 2017 ISSCR Annual Meeting
  • Int'l Joint Research
• [Presentation] Analysis of a novel gene expressed by S100β-positive cells in the rat anterior lobe of the pituitary (2017)
  • Author(s): Horiguchi, K., Nakakura, T., Tsukada, T., Yoshida, S., Hasegawa, R., Takigami, S., Ohsako, S., Kato, T., Kato, Y
  • Organizer: WCRB 2017
  • Int'l Joint Research
• [Presentation] 下垂体の幹・前駆細胞の多様性 (2017)
  • Author(s): 加藤幸雄、上春浩貴、吉田彩舟、加藤たか子
  • Organizer: 第90回日本内分泌学会学術集会
• [Presentation] 下垂体前葉内濾胞星状細胞の新規マーカーの探索 (2017)
  • Author(s): 堀口幸太郎、吉田彩舟、藤原研、塚田岳大、加藤たか子、長谷川瑠美、周瀧、大迫俊二、屋代隆、加藤幸雄
  • Organizer: 第90回日本内分泌学会学術集会
• [Presentation] 成体下垂体の実質層に存在する幹・前駆細胞ニッチの解析 (2017)
  • Author(s): 吉田彩舟、百合野秀朗、小林正明、矢野健太郎、橋本真一、加藤たか子、加藤幸雄
  • Organizer: 第32回日本下垂体研究会学術集会
• [Presentation] 下垂体前葉のS100β陽性細胞が発現するCD抗原の解析 (2017)
  • Author(s): 堀口幸太郎、吉田彩舟、藤原研、塚田岳大、加藤たか子、長谷川瑠美、周瀧、大迫俊二、屋代隆、加藤幸雄
  • Organizer: 第32回日本下垂体研究会学術集会
• [Presentation] 下垂体由来株化細胞TtT/GFの分化能の検討とTGFbの関与 (2016)
  • Author(s): 塚田岳大, 吉田彩舟, 紀藤圭治, 藤原研, 八子英司, 堀口幸太郎, 屋代隆, 加藤たか子, 加藤幸雄
  • Organizer: 第41回日本比較内分泌学会大会
  • Place of Presentation: 北里大学
  • Year and Date: 2016-12-09
• [Presentation] レチノイン酸シグナルによる下垂体特異的転写因子Prop1の転写制御機構の解析 (2016)
  • Author(s): 西原大翔, 吉田彩舟, 藤原研, 菅野尚子, 上春浩貴, 加藤たか子, 屋代隆, 加藤幸雄
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] 成体下垂体に存在する幹・前駆細胞ニッチの単離と分化能の解析 (2016)
  • Author(s): 吉田彩舟, 西村直人, 菅野尚子, 西原大翔, 上春浩貴, 加藤たか子, 加藤幸雄
  • Organizer: 第109回日本繁殖生物学会大会
  • Place of Presentation: 麻布大学
  • Year and Date: 2016-09-11
• [Presentation] ラット下垂体前葉内TSH産生細胞における細胞表面抗原CD90の発現 (2016)
  • Author(s): 堀口幸太郎, 中倉敬, 吉田彩舟, 長谷川瑠美, 瀧上周, 大迫俊二, 加藤たか子, 加藤幸雄
  • Organizer: 第109回日本繁殖生物学会大会
  • Place of Presentation: 麻布大学
  • Year and Date: 2016-09-11
• [Presentation] レチノイン酸シグナルによる転写因子Prop1の転写制御機構の解析 (2016)
  • Author(s): 西原大翔, 吉田彩舟, 藤原研, 加藤たか子, 屋代隆, 加藤幸雄
  • Organizer: 第109回日本繁殖生物学会大会
  • Place of Presentation: 麻布大学
  • Year and Date: 2016-09-11
• [Presentation] Regulatory of pituitary specific transcription factor Prop1 by retinoic acid signaling (2016)
  • Author(s): Nishihara H, Yoshida S, Fuziwara K, Kanno N, Ueharu H, Kato T, Yashiro T, Kato Y
  • Organizer: International Symposium on Pituitary Gland and Related Systems (ISPGRS 2016)
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2016-09-01
  • Int'l Joint Research
• [Presentation] Neuronatin progresses cell differentiation by participating in regulation of intracellular Ca2+-level (2016)
  • Author(s): Kanno N, Yoshida S, Ueharu H, Kato T, Kato Y
  • Organizer: International Society for Stem Cell Research (ISSCR2016)
  • Place of Presentation: San Francisco
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] SOX10-postiive cells emerge in the rat pituitary gland from the late embryonic stage and settle in the postnatal pituitary as stem/progenitor cells (2016)
  • Author(s): Ueharu H, Yoshida S, Kanno N, Nishimura1 N, Kato T, Kato Y
  • Organizer: International Society for Stem Cell Research (ISSCR2016)
  • Place of Presentation: San Francisco
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] Isolation and characterization of adult stem/progenitor cell niche located in the parenchyma of the rat pituitary gland (2016)
  • Author(s): oshida S, Nishimura N, Kato T, Kato Y
  • Organizer: International Society for Stem Cell Research (ISSCR2016)
  • Place of Presentation: San Francisco
  • Year and Date: 2016-06-22
  • Int'l Joint Research
• [Presentation] 成体下垂体前葉に存在する幹・前駆細胞ニッチの単離と制御機構の解析 (2016)
  • Author(s): 吉田彩舟, 加藤たか子, 加藤幸雄
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2016-04-21
  • Invited
• [Presentation] 細胞表面抗原CD90を利用したラット下垂体前葉からのTSH産生細胞の単離 (2016)
  • Author(s): 堀口幸太郎, 吉田彩舟, 菅野尚子, 上春浩貴, 陳默, 長谷川瑠美, 加藤たか子, 周 瀧, 大迫俊二, 加藤幸雄
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 京都国際会館
  • Year and Date: 2016-04-21
• [Presentation] 成体下垂体に存在する幹・前駆細胞ニッチの単離と解析. (2016)
  • Author(s): 吉田彩舟、西村直人、上春浩貴、菅野尚子、陳默、加藤たか子、加藤幸雄
  • Organizer: 第15回日本再生医療学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2016-03-17
• [Presentation] ヒト男性不妊におけるヘルペスウイルス感染解析 (2016)
  • Author(s): 陳默、西村直人、蔡立義、王洪華、和泉俊一郎、加藤たか子、加藤幸雄.
  • Organizer: 第20回日本生殖内分泌学会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2016-01-09
• [Presentation] 新生仔マウス脳で発見されたNeuronatinのラット精巣における局在解析. (2015)
  • Author(s): 菅野尚子、陳默、樋口雅司、加藤たか子、加藤幸雄.
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 成体下垂体前葉に存在する幹・前駆細胞ニッチの単離と解析. (2015)
  • Author(s): 西村直人、吉田彩舟、染谷昌亮、西原大翔、加藤たか子、加藤幸雄.
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 下垂体におけるSOX10陽性細胞の時空間的局在とその特性解析. (2015)
  • Author(s): 上春浩貴、西村直人、吉田彩舟、菅野尚子、西原大翔、加藤たか子、加藤幸雄.
  • Organizer: 第38回日本分子生物学会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Neuronatin emerges in the rat pituitary stem/progenitor cells and finishes its role in the terminally differentiating cells. (2015)
  • Author(s): Naoko Kanno, Masashi Higuchi, Saishu Yoshida, Hideji Yako, Mo Chen, Hiroki Ueharu, Naoto Nishimura, Takako Kato, Yukio Kato.
  • Organizer: Society for Endocrinology BES 2015
  • Place of Presentation: Edinburgh, UK
  • Year and Date: 2015-11-02
  • Int'l Joint Research