The analysis of the hypoxia-induced regulation mechanism in erythropetin gene expression and erythrocytosis

• Project/Area Number: 22790895
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: OBARA Naoshi 筑波大学, 医療医学系, 講師 (70422178)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Notchシグナル / Nestin / エリスロポエチン / 造血不全 / ストローマ細胞 / 赤血球造血

Research Abstract

Recently, the possibility has been suggested that there are bone marrow stromal cells expressing Nestin genes which are neural stem cell markers and that those cells play an important role in hematopoiesis. Therefore, we crossbred RBP-J conditional-knockout mice. RBP-J are downstream genes of Notch signaling. and NestinCre mice and analyzed the hematopoiesis of those mice with which Nestin-expressing-cell-specific RBP-J signaling was knocked out. The fetuses of the knockout mice suffered from severe anemia during embryonic stage, the differentiation of their erythroblasts was impaired and the onset of erythropoietin was significantly lowered. The erythropoietin productive cells of fetal livers developed Nestin and it was suggested that stromal cells of fetal livers may be important to hematopoietic differentiation.

Research Products

• [Journal Article] Nine years interval between first and second bone marrow transplantations and subsequent long-term survival-a case of acute myeloid leukemia with MLL-AF6 fusion gene (2011)
  • Author(s): Yokoyama Y, Suzukawa K, Okoshi Y, Nanmoku T, Obara N, Enami T, Hasegawa Y, Chiba S
  • Journal Title: Annals of Hematology Volume: 91 Issue: 9 Pages: 1491-1493
  • DOI: 10.1007/s00277-012-1417-2
  • Peer Reviewed
• [Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia (2011)
  • Author(s): Kenichi Yoshida
  • Journal Title: Nature Volume: 478 Issue: 7367 Pages: 64-69
  • DOI: 10.1038/nature10496
  • Peer Reviewed
• [Journal Article] Specific contribution of the erythropoietin gene 3' enhancer to hepatic erythropoiesis after late embryonic stages (2011)
  • Author(s): Suzuki N, Obara N, Pan X, Watanabe M, Jishage K-i, Minegishi N, Yamamoto M
  • Journal Title: Mol Cell Biol Volume: 31 Issue: 18 Pages: 3896-3905
  • DOI: 10.1128/mcb.05463-11
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Cui S, Kolodziej KE, Obara N, Amaral-Psarris A, Demmers J, Shi L, Engel JD, Grosveld F, Strouboulis J, Tanabe O
  • Journal Title: Molecular cell biology Volume: 31 Issue: 16 Pages: 3298-3331
  • DOI: 10.1128/mcb.05310-11
  • Peer Reviewed
• [Journal Article] 巨赤芽球性貧血 (2010)
  • Author(s): 小原直、二宮治彦
  • Journal Title: 治療 Volume: 92 Pages: 2333-2338
• [Presentation] Effect and safety of rabbit anti-thymocyte globulin (ATG) for aplastic anemia (2011)
  • Author(s): Tatsuhiro Sakamoto, Naoshi Obara, RieMatsubara, Kuniyoshi Fukuda, MayukoKoshino, Naoski Kurita, Hedekazu Nishikii, Yasuhisa Yokoyama, Mamiko Sakata, YasuhiOkoshi, Kazumi Suzukawa, Yuichi Hasegawa, Shigeru Chiba
  • Organizer: 日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] Outcomes of splenectomy for adult patients with ITP-a single center retrospective analysis (2011)
  • Author(s): Yasushi Okoshi, Naoki Kurita, Hidekazu Nishikii, Yasuhisa Yokoyama, Mamiko Sakata-Yanagimoto, Naoshi Obara, Kazumi Suzukawa, Yuichi Hasegawa, Shigeru Chiba
  • Organizer: 日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] 静注Busulfanによる前処置後の移植後胃前庭部毛細血管拡張症 (2011)
  • Author(s): 福田匡芳, 栗田尚樹, 坂本竜弘, 錦井秀和, 横山泰久, 坂田-柳元麻実子, 小原直, 大越靖, 鈴川和己, 長谷川雄一, 千葉滋
  • Organizer: 日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] Effect and safety of rabbit anti-thymocyte globulin (ATG)for aplastic anemia (2011)
  • Author(s): Tatsuhiro Sakamoto, Naoshi Obara, Rie Matsubara, Kuniyoshi Fukuda, Mayuko Koshino, Naoski Kurita, Hedekazu Nishikii, Yasuhisa Yokoyama, Mamiko Sakata, Yasuhi Okoshi, Kazumi Suzukawa, Yuichi Hasegawa, Shigeru Chiba
  • Organizer: 日本血液学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] 発症から8年経過し再発後の治療が奏功しているT細胞性中枢神経原発 (2011)
  • Author(s): 真家紘一郎、鈴川和己、坂本竜弘、福田匡芳、日下部学、鈴木幸恵、栗田尚樹、錦井秀和、横山泰久、小原直、大越靖、長谷川雄一、千葉滋
  • Organizer: 第166回日本血液学会例会
  • Place of Presentation: 東京
  • Year and Date: 2011-07-02
• [Presentation] Detection of CD55-and CD59-negative immature reticulocytes may improves sensitivity/specificity to identify aminor population of PNH-type cells in patients with myelodysplastic syndrome/aplastic anemia (2011)
  • Author(s): 小原直, 佐藤晶子, 千葉滋, 二宮治彦
  • Organizer: 第2回JSH国際シンポジウム
  • Place of Presentation: 長崎
  • Year and Date: 2011-04-13
• [Presentation] Detection of CD55-and CD59-negative immature reticulocytes may improves sensitivity/specificity to identify a minor population of PNH-type cells in patients with myelodysplastic syndrome/aplastic anemia (2011)
  • Author(s): 小原直、佐藤晶子、千葉滋、二宮治彦
  • Organizer: 第2回JSH国際シンポジウム
  • Place of Presentation: 長崎
  • Year and Date: 2011-04-13
• [Presentation] Adverse effecs of intravenous morphine and fentanyl for stomatitis in patients receiving allogenic HCT a single center retrospective analysis (2011)
  • Author(s): 越野繭子, 大越靖, 坂本竜弘, 福田匡芳, 松原理絵, 栗田尚樹, 錦井秀和, 横山泰久, 坂田麻実子, 小原直, 鈴川和己, 長谷川雄一, 千葉滋
  • Organizer: 日本造血幹細胞移植学会
  • Place of Presentation: 松山
  • Year and Date: 2011-03-09
• [Presentation] 静注Busulfn/Cyclophosphamideを移植前処置に用いた同種造血幹細胞移植11例の検討 (2011)
  • Author(s): 栗田尚樹, 大越靖, 福田匡芳, 松原理絵, 坂本竜弘, 錦井秀和, 横山泰久, 坂田麻実子, 小原直, 鈴川和己, 長谷川雄一, 千葉滋
  • Organizer: 日本造血幹細胞移植学会
  • Place of Presentation: 松山
  • Year and Date: 2011-03-09
• [Presentation] Acute panmyelosis with myelofibrosisに対し同種造血幹細胞が有用であった1例 (2011)
  • Author(s): 松原理絵, 小原直, 坂本竜弘, 福田匡芳, 越野繭子, 栗田尚樹, 錦井秀和, 横山泰久, 坂田-柳元麻実子, 大越靖, 鈴川和己, 長谷川雄一, 千葉滋
  • Organizer: 第165回日本血液学会例会
  • Place of Presentation: 東京
  • Year and Date: 2011-02-05
• [Presentation] Dentification of components of globin gene repressor, DRED (2010)
  • Author(s): Naoshi Obara, Katarzyna Kolodziej, Osamu Tanabe, Flank Grosveld, John Stroubolius, James Douglas Engel
  • Organizer: 日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] Retrospective analysis of BCL2+DLBCL in the rituximab era : multi-center analysis (2010)
  • Author(s): Hidekazu Nishikii, Naoya Nakamura, Yuzuru Kondou, Minoru Kojima, Jun Takizawa, Yuichi Hasegawa, Yasushi Okoshi, Kazumi Suzukawa, Yasuhisa Yokoyama, Naoshi Obara, Mamko Sakata-Yanagimoto, Masayuki Noguchi, Sadao Aoki, Kiyoshi Andou, Shigeru Chiba
  • Organizer: 日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] Characterization of co-repressor complex DRED in globin gene expression (2010)
  • Author(s): Naoshi Obara, Katarzyna Kolodziej, Osamu Tanabe, Flank Grosveld, John Stroubolius, James Douglas Engel
  • Organizer: The 1st JSH International Symposium 2010
  • Place of Presentation: Akita
  • Year and Date: 2010-06-25
• [Presentation] Profiling of mul tiple gene mutations in myelodysplasti c syndromes using high-throughput reseq uenceing combined with barcode labeling (2010)
  • Author(s): Yasunobu Nagata, Masashi Sanada, Kenichi Yoshida, Takeo Nakaya, Aiko Matsubara, Naoshi Obara, Ken Ishiyama Shuichi Miyawaki, Junko Takita, Shigeru Chiba, Lee-Yung Shih, H Phillip Koeffler, Seishi Ogawa
  • Organizer: The American Society of Hematology 52nd Annual Meeting
  • Place of Presentation: Orland, USA
• [Presentation] Who le exome analysis of myelodysplastic syndromes using next-generation reseq uencing technology (2010)
  • Author(s): Kenichi Yoshida, Masashi Sanada, Yasunobu Nagata, Ryouichiro Kawahata, Motohiro Kato, Aiko Matsubara, Junko Takita, Hirano Mori, Ken Ishiyama, Taka yuki Ishikawa, Shuichi Miyawaki, Naoshi Obara, Shigeru Chiba, Seishi Ogawa
  • Organizer: The American So ciety of Hematology 52nd Annual Meeting
  • Place of Presentation: Orland, USA