Analysis of Nestin expressing cells in bone marrow

• Project/Area Number: 25461408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: Obara Naoshi 筑波大学, 医学医療系, 准教授 (70422178)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 造血支持細胞 / Nestin / 造血不全 / 造血幹細胞 / Ｎｅｓｔｉｎ / Ｎｏｔｃｈシグナル / 血管内皮細胞 / Notchiシグナル

Outline of Final Research Achievements

Bone marrow stromal cells that express nestin are proposed to play a fundamental role in hematopoiesis. However, the molecular mechanism operating in nestin-expressing cells to support hematopopoiesis remain to be clarified.To approach this issue, we established The nestin-CreERT2-RBP-Jκflox/flox (CKO) mice. The CKO mice showed mild anemia, and marked splenomegaly. Mature erythroblasts in the bone marrow of CKO mice decreased, but oppositely increased in the spleen compared to the wild type. Immature erythroid cells increased in bone marrow of CKO mice compared to the wild type. These results showed that if Notch signaling in nestin-expressing cells is knocked out, erythropoiesis in the bone marrow decreases, and be compensated by the spleen. Our results indicate that nestin-expressing hematopoietic-supporting cells are important to support erythropoiesis and select hematopoietic tissues. Furthermore, we think that Notch signaling is involved in regulating erythropoiesis.

Research Products

• [Journal Article] A nationwide survey of co-occurrence of malignant lymphomas and myelodysplastic syndromes/myeloproliferative neoplasms. (2016)
  • Author(s): Sakata-Yanagimoto M, Yokoyama Y, Muto H, Obara N, Kurita N, Kato T, Hasegawa Y, Miyazaki Y, Kurokawa M, Chiba S
  • Journal Title: Annals of Hematology. Volume: 98 Pages: 829-30
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Late occurrence of Epstein-Barr virus-associated lymphoproliferative disorder in a patient with follicular lymphoma treated with bendamustine and rituximab. (2015)
  • Author(s): Muroi K, Sakata-Yanagimoto M, Sato T, Yokoyama Y, Maie K, Kurita N, Obara N, Hasegawa Y, Noguchi M, Chiba S.
  • Journal Title: Ann Hematol Volume: 94 Pages: 2061-2062
  • DOI: 10.1007/s00277-015-2463-3
  • NAID: 120006478267
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Improvement of Renal Function by Long-Term Sustained Eculizumab Treatment in a Patient with Paroxysmal Nocturnal Hemoglobinuria. (2015)
  • Author(s): Ninomiya H, Obara N, Niiori-Onishi A, Yokoyama Y, Sakata-Yanagimoto M, Hasegawa Y, Chiba S
  • Journal Title: Case Rep Hematol Volume: 673195 Pages: 1-4
  • DOI: 10.1155/2015/673195
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Complete Remission in Systemic Skin Interdigitating Dendritic Cell Sarcoma after ABVD Chemotherapy (2015)
  • Author(s): Kyogoku C, Seki M, Ogawa S, Miyamoto K, Ito Y, Kurita N, Yokoyama Y, Sakata-Yanagimoto M, Obara N, Hasegawa Y, Fujishima F, Ichinohasama R, Nakamura S, Chiba S.
  • Journal Title: J Clin Exp Hematopathol Volume: 55 Issue: 1 Pages: 33-37
  • DOI: 10.3960/jslrt.55.33
  • NAID: 130005083796
  • ISSN: 1346-4280
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of a fusion gene composed of a Hippo pathway gene MST2 and a common translocation partner ETV6 in a recurrent translocation t(8;12)(q22;p13) in acute myeloid leukemia. (2015)
  • Author(s): Ogawa S, Yokoyama Y, Suzukawa K, Nanmoku T, Kurita N, Seki M, Maie K, Suyama T, Takaiwa N, Sakata-Yanagimoto M, Obara N, Hasegawa Y, Chiba S
  • Journal Title: Ann Hematol Volume: 94 Pages: 1431-1433
  • DOI: 10.1007/s00277-015-2391-2
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Double somatic mosaic mutations in TET2 and DNMT3A--origin of peripheral T cell lymphoma in a case. (2015)
  • Author(s): Nguyen TB, Sakata-Yanagimoto M, Nakamoto-Matsubara R, Enami T, Ito Y, Kobayashi T, Obara N, Hasegawa Y, Chiba S
  • Journal Title: Ann Hematol Volume: EPUB ahead of print Pages: 1221-1223
  • DOI: 10.1007/s00277-015-2332-0
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acute painful crisis in a female Nigerian patient with sickle cell disease (2015)
  • Author(s): Nin S, Seki M, Maie K, Kuroda A, Miyamoto K, Ogawa S, Ito Y, Kurita N, Yokoyama Y, Sakata Yanagimoto M, Obara N, Hasegawa Y, Ogino Y, Ito T, Chiba S.
  • Journal Title: Jpn. J. Clin. Hematol. Volume: 56(1) Issue: 1 Pages: 30-34
  • DOI: 10.11406/rinketsu.56.30
  • NAID: 130004920690
  • ISSN: 0485-1439
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Multiple myeloma recurring as small intestinal polyposis after autologous hematopoietic stem cell transplantation (2015)
  • Author(s): Otsu K, Seki M, Ogawa S, Miyamoto K, Ito Y, Sakata A, Kurita N, Yokoyama Y, Sakata-Yanagimoto M, Obara N, Hasegawa Y, Chiba S
  • Journal Title: Jpn. J. Clin. Hematol. Volume: 56 Issue: 4 Pages: 400-405
  • DOI: 10.11406/rinketsu.56.400
  • NAID: 130005069840
  • ISSN: 0485-1439
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acute myeloid leukemia possibly originating from the same clone of testicular germ cell tumor (2013)
  • Author(s): Suyama T, Obara N, Kawai K, Yamada K, Kusakabe M, Kurita N, Nishikii H, Yokoyama Y, Suzukawa K, Hasegawa Y, Noguchi M, Chiba S
  • Journal Title: Rinsho Ketsueki Volume: 54 Pages: 764-768
  • NAID: 10031196294
  • Peer Reviewed
• [Journal Article] Effectiveness and safety of rabbit anti-thymocyte globulin in Japanese patients with aplastic anemia (2013)
  • Author(s): Sakamoto T, Obara N, Kurita N, Sakata-Yanagimoto M, Nishikii H, Yokoyama Y, Suzukawa K, Hasegawa Y, Chiba S.
  • Journal Title: Int J Hematol. Volume: 98 Pages: 319-322
  • DOI: 10.1007/s12185-013-1418-5
  • Peer Reviewed
• [Journal Article] Recurrent mutations in multiple components of the cohesin complex inmyeloid neoplasms (2013)
  • Author(s): Kon A, Yoshida K
  • Journal Title: Nature Genetics Volume: 45 Pages: 1232-1237
  • DOI: 10.1038/ng.2731
  • Peer Reviewed
• [Journal Article] Perisurgical induction of eculizumab in a patient with paroxysmal nocturnal hemoglobinuria: its inhibition of surgery-triggered hemolysis and the consequence of subsequent discontinuation (2013)
  • Author(s): Kurita N, Obara N, Fukuda K, Nishikii H, Sato S, Inagawa S, Kurokawa T, Owada Y, Ninomiya H, Chiba S
  • Journal Title: Blood Coagul Fibrinolysis Volume: 24 Pages: 658-662
  • DOI: 10.1097/mbc.0b013e328360d057
  • Peer Reviewed
• [Presentation] NOTCH signaling pathway in bone marrow nestin-expressing cells controls balance of erythropoiesis between bone marrow and spleen (2016)
  • Author(s): TATSUHIRO SAKAMOTO
  • Organizer: 幹細胞シンポジウム
  • Place of Presentation: 淡路夢舞台国際会議場
  • Year and Date: 2016-05-20
• [Presentation] Abnormalities in nestin-expressing bone marrow stromal cells in myelodysplastic syndromes (2015)
  • Author(s): NAOSHI OBARA
  • Organizer: International Society for Experimental Hematology 44th Annual Scientific Meeting
  • Place of Presentation: 京都l国際会館
  • Year and Date: 2015-09-17
  • Int'l Joint Research
• [Presentation] Abnormalities in nestin-expressing bone marrow stromal cells in myelodysplastic syndromes (2015)
  • Author(s): NAOSHI OBARA
  • Organizer: The 6th JSH International Symposium 2015
  • Place of Presentation: 軽井沢プリンスホテル
  • Year and Date: 2015-05-22
  • Int'l Joint Research / Invited
• [Presentation] Abnormalities in nestin-expressing bone marrow stromal cells in myelodysplastic syndromes (2015)
  • Author(s): Naoshi Obara
  • Organizer: JSH国際シンポジウム
  • Place of Presentation: 軽井沢
  • Year and Date: 2015-05-22
• [Presentation] Localization of nestin-expressing cells in bone marrow and the role of Notch signaling in nestin-expressing stromal cells in hematopoiesis (2014)
  • Author(s): Naoshi Obara
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31
• [Presentation] The OPTIMA update: baseline assessment of PNH-type cells in patients with bone marrow failure (2013)
  • Author(s): Yuji Yonemura, Tatsuya Kawaguchi, Kohei Hosokawa, Chiharu Sugimori, Masaki Yamamoto, Naoshi Obara, Hideyoshi Noji, Yoshihiko Nakamura, Kiyoshi Ando, Tsutomu Shichishima, Haruhiko Ninomiya, Shigeru Chiba, Jun-ichi Nishimura, Yuzuru Kanakura, Shinji Nakao
  • Organizer: 日本血学会
  • Place of Presentation: 札幌
• [Presentation] Baseline assessment of PNH-type cells in patients with bone marrow failure (The OPTIMA study) (2013)
  • Author(s): Naoshi Obara, Shigeru Chiba, Kohei Hosokawa, Chiharu Sugimori, Masaki Yamamoto, Hideyoshi Noji, Yuji Yonemura, Yoshihiko Nakamura, Kiyoshi Ando, Tatsuya Kawaguchi, Tsutomu Shichishima, Haruhiko Ninomiya, Jun-ichi Nishimura, Yuzuru Kanakura, Shinji Nakao
  • Organizer: アメリカ血液学会
  • Place of Presentation: ニューオーリンズ
• [Book] 血液内科 (2013)
  • Author(s): 小原 直
  • Total Pages: 5
  • Publisher: 科学評論社
• [Book] 血液症候群(第2版)-Imersland-Grasbeck症候群（選択的ビタミンB12吸収不全症） (2013)
  • Author(s): 小原 直、二宮 治彦
  • Total Pages: 2
  • Publisher: 日本臨床社
• [Book] 血液症候群(第2版)-若年性悪性貧血 (2013)
  • Author(s): 小原 直、二宮 治彦
  • Total Pages: 3
  • Publisher: 日本臨床社
• [Book] 血液症候群(第2版)-ホルムイミノトランスフェラーゼ欠損症 (2013)
  • Author(s): 小原 直、二宮 治彦
  • Total Pages: 3
  • Publisher: 日本臨床社