Elucidation of the epigenetic regulatory network during cell differentiation of spermatogonial stem cells

• Project/Area Number: 25462541
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Nagoya City University
• Principal Investigator: Azemoto Masataka 名古屋市立大学, 医学(系)研究科(研究院), 研究員 (70264736)
• Co-Investigator(Kenkyū-buntansha): KAMISAWA HIDEYUKI 名古屋市立大学, 大学院医学研究科, 研究員 (00551277) ; NISHIO HIDENORI 名古屋市立大学, 大学院医学研究科, 助教 (10621063) ; KOHRI KENJIRO 名古屋市立大学, 学長 (30122047) ; HAYASHI YUTARO 名古屋市立大学, 大学院医学研究科, 准教授 (40238134) ; KOJIMA YOSHIYUKI 福島県立医科大学, 医学部, 教授 (60305539) ; 水野 健太郎 名古屋市立大学, 医学(系)研究科(研究院), 講師 (70448710)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 精子幹細胞 / エピゲノム / 精巣腫瘍 / 細胞分化

Outline of Final Research Achievements

Recently, epigenetic regulation has benn regarded as an important system of gene regulation. There are DNA methylation or histone modification as typical regulatory system, and it seems that epigenome is involved in the determination of cell fate. From the results of our previous work, we considered that the dysfunction of spermatogonial stem cells is one of the reasons why spermatogenesis is disrupted in cryptorchidism. In the present research, we aimed the specific epigenetic regulatory network during cell differentiation of spermatogonial stem cells. We assessed the spermatogonial stem cells in the testes of each developmental stages using experimental animals. As a result, we detected that Kdm5a, demethylase for histone H3K4, and miR-135a (microRNA) are involved in differentiation of spermatogonial stem cells.

Research Products

• [Journal Article] Novel splice site mutation in MAMLD1 in a patient with hypospadias. (2015)
  • Author(s): 10.1038/ejhg.2015.13
  • Journal Title: Sex Dev Volume: 3 Issue: 3 Pages: 1-1
  • DOI: 10.1159/000380842
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Clear cell sarcoma of the kidney distinguished from synovial sarcoma of the kidney by genetic analysis (2015)
  • Author(s): Hirose M, Mizuno K, Kamisawa H, Nishio H, Moritoki Y, Kohri K, Hayashi Y.
  • Journal Title: BMC Research Notes Volume: 8 Issue: 1 Pages: 129-133
  • DOI: 10.1186/s13104-015-1100-5
  • Peer Reviewed / Open Access
• [Journal Article] Proinflammatory and Metabolic Changes Facilitate Renal Crystal Deposition in an Obese Mouse Model of Metabolic Syndrome. (2015)
  • Author(s): Taguchi K, Okada A, Hamamoto S, Iwatsuki S, Naiki T, Ando R, Mizuno K, Tozawa K, Kohri K, Yasui T.
  • Journal Title: J Urol. Volume: 194 Issue: 6 Pages: 1787-96
  • DOI: 10.1016/j.juro.2015.07.083
  • Peer Reviewed / Open Access
• [Journal Article] First case report of staghorn calculi successfully removed by mini-endoscopic combined intrarenal surgery in a 2-year-old boy. (2015)
  • Author(s): Taguchi Kazumi, Hamamoto Shuzo, Okada Atsushi, Mizuno Kentaro, Tozawa Keiichi, Hayashi Yutaro, Kohri Kenjiro, Yasui Takahiro
  • Journal Title: International Journal of Urology Volume: 22 Issue: 10 Pages: 978-80
  • DOI: 10.1111/iju.12860
  • Peer Reviewed
• [Journal Article] Laparoscopic modified bypass pyeloplasty: a simple procedure for straightforward ureteral spatulation and intracorporeal suturing (2015)
  • Author(s): Haga N, Sato Y, Ogawa S, Yabe M, Akaihata H, Hata J, Ishibashi K, Mizuno K, Hayashi Y, Kojima Y
  • Journal Title: International Urology and Nephrology Volume: 47 Issue: 12 Pages: 1933-1938
  • DOI: 10.1007/s11255-015-1123-9
  • Peer Reviewed
• [Journal Article] Expression profiling of microRNAs in cryptorchid testes : miR-135a contributes to the maintenance of spermatogonial stem cells by regulating FoxO1 (2014)
  • Author(s): Moritoki Y, Hayashi Y, Mizuno K, Kamisawa H, Nishio H, Kurokawa S, Ugawa S, Kojima Y, Kohri K
  • Journal Title: J Urol Volume: 191 Issue: 4 Pages: 1174-80
  • DOI: 10.1016/j.juro.2013.10.137
  • Peer Reviewed / Open Access
• [Journal Article] Expression analysis of the pluripotency marker UTF-1 for determining the applicability of testis-sparing surgery for prepubertal testis tumors. (2013)
  • Author(s): Mizuno K, Hayashi Y, Kamisawa H, Nishio H, Moritoki Y, Kohri K.
  • Journal Title: Journal of Pediatric Surgery Case Report Volume: １ Pages: 125-128
  • Peer Reviewed
• [Journal Article] Gene expression profile during testicular development in patients with SRY-negative 46, XX testicular disorder of sex development (2013)
  • Author(s): Mizuno K, Kojima Y, Kamisawa H, Moritoki Y, Nishio H, Kohri K, Hayashi Y
  • Journal Title: UROLOGY Volume: 82: 1453 Issue: 6 Pages: 1453-1453
  • DOI: 10.1016/j.urology.2013.08.040
  • Peer Reviewed
• [Journal Article] Cryptic genomic rearrangements in three patients with 46,XY disorders of sex development (2013)
  • Author(s): M. Igarashi, V. C. Dung, E. Suzuki, S. Ida, M. Nakacho, K. Nakabayashi, K. Mizuno, Y. Hayashi, K. Kohri, Y. Kojima, T. Ogata, M. Fukami
  • Journal Title: PLoS. One Volume: 8 Issue: 7 Pages: e68194-e68194
  • DOI: 10.1371/journal.pone.0068194
  • Peer Reviewed
• [Presentation] Elucidation of regulatory mechanisms during differentiation of spermatogonial stem cell via androgen action (2015)
  • Author(s): Mizuno K, Hayashi Y, Kamisawa H, Moritoki Y, Nishio H, Kurokawa S, Nakane A, Maruyama T, Yasui T
  • Organizer: 26th European Society of Pediatric Urology Congress
  • Place of Presentation: プラハ市（チェコ共和国）
  • Year and Date: 2015-10-14
  • Int'l Joint Research
• [Presentation] Feasibility of laparoscopic orchiopexy for intracanalicular testes in comparative study of surgical outcome with open transinguinal orchiopexy (2015)
  • Author(s): Mizuno K, Hayashi Y, Kamisawa H, Moritoki Y, Nishio H, Kurokawa S, Nakane A, Maruyama T, Yasui T
  • Organizer: 26th European Society of Pediatric Urology Congress
  • Place of Presentation: プラハ市（チェコ共和国）
  • Year and Date: 2015-10-14
  • Int'l Joint Research
• [Presentation] 停留精巣が男性不妊症に至る機序とは～閉塞性無精子症患者の精巣検体を用いた研究～ (2015)
  • Author(s): 神沢 英幸、水野 健太郎、西尾 英紀、守時 良演、岩月 正一郎、黒川 覚史、梅本 幸裕、佐々木 昌一、林 祐太郎、安井 孝周
  • Organizer: 第34回日本アンドロロジー学会学術大会
  • Place of Presentation: 福岡大学病院（福岡県福岡市）
  • Year and Date: 2015-06-26
• [Presentation] ヒストンタンパク脱メチル酵素KDM5Aによるヒト停留精巣での造精機能障害機序の解明 (2015)
  • Author(s): 西尾 英紀、水野 健太郎、神沢 英幸、守時 良演、最上 徹、岩月 正一郎、梅本 幸裕、佐々木 昌一、林 祐太郎、安井 孝周
  • Organizer: 第34回日本アンドロロジー学会学術大会
  • Place of Presentation: 福岡大学病院（福岡県福岡市）
  • Year and Date: 2015-06-26
• [Presentation] ヒストンタンパク脱メチル化酵素KDM5Aのヒト造精機能障害への関与 (2015)
  • Author(s): 西尾 英紀、水野 健太郎、神沢 英幸、守時 良演、最上 徹、林 祐太郎、郡 健二郎
  • Organizer: 第103回日本泌尿器科学会総会
  • Place of Presentation: 石川県立音楽堂、ANAクラウンプラザホテル金沢 他（石川県金沢市）
  • Year and Date: 2015-04-18
• [Presentation] 精巣発生における細胞接着制御Rhoシグナル伝達系の機能解析 (2013)
  • Author(s): 水野健太郎、神沢英幸、守時良演、西尾英紀、林祐太郎、郡健二郎
  • Organizer: 第101回日本泌尿器科学会総会
  • Place of Presentation: さっぽろ芸術文化の館（札幌）
• [Presentation] 骨盤内異形成腎と腹腔内精巣を合併した一例 ～発症要因の組織学的考察～ (2013)
  • Author(s): 水野健太郎、西尾英紀、林祐太郎、郡健二郎
  • Organizer: 第22回 日本小児泌尿器科学会総会
  • Place of Presentation: 東京ビッグサイトTFTホール（東京）
• [Presentation] 精子幹細胞分化におけるアンドロゲンの役割 (2013)
  • Author(s): 水野健太郎、神沢英幸、守時良演、西尾英紀、岩月正一郎、梅本幸裕、佐々木昌一、林祐太郎、郡健二郎
  • Organizer: 日本アンドロロジー学会第32回学術大会
  • Place of Presentation: グランキューブ大阪（大阪）
• [Presentation] ゲノムワイド解析を用いた精巣発生メカニズムの解明 (2013)
  • Author(s): 水野健太郎、神沢英幸、守時良演、西尾英紀、林祐太郎、郡健二郎
  • Organizer: 第64回名古屋市立大学医学会総会
  • Place of Presentation: 名古屋市立大学（名古屋）