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

2011 Fiscal Year Final Research Report

• 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
• 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
  • DOI: DOI:10.1007/s00277-012-1417-2
  • Peer Reviewed
• [Journal Article] Frequent pathway mutations of splicing machinery in myelodysplasia., Nature (2011)
  • Author(s): Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H, Miyano S, Ogawa S
  • Volume: 478
  • Pages: 64-69
  • DOI: DOI:10.1038/nature10496
  • Peer Reviewed
• [Journal Article] (2011)
  • Author(s): Suzuki N, Obara N, Pan X, Watanabe M, Jishage K, Minegishi N, Yamamoto M
  • Journal Title: Molecular cell biology Volume: 31 Pages: 3896-3905
  • DOI: 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 Pages: 3298-3331
  • DOI: DOI:10.1128/MCB.05310-11
  • Peer Reviewed
• [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] 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] 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] 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
  • Year and Date: 20101204-07
• [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
  • Year and Date: 20101204-07