Disease modeling of mosaic CINCA syndrome with iPS cells

• Project/Area Number: 25461591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: Saito Megumu 京都大学, iPS細胞研究所, 准教授 (90535486)
• 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: CINCA症候群 / 体細胞モザイク / iPS細胞

Outline of Final Research Achievements

Taking advantage of iPS cells from CINCA syndrome patients with somatic mosaicism, we aimed at 1) exploring the pathogenic mechanism of somatic mosaicism, and investigating the function of compounds that might inhibit the activity of NLRP3 inflammasome.As a result, 1) our data suggested that the somatic ontogeny might be tracked using iPS cells, 2) we established a screening system using iPS cell-derived monocytic cells and monocytic cell lines.

Research Products

• [Journal Article] 血液・免疫疾患のiPS細胞研究 (2016)
  • Author(s): 齋藤潤、中畑龍俊
  • Journal Title: 細胞 Volume: 48 Pages: 65-68
• [Journal Article] 臨床応用を目指した基礎研究 疾患モデル細胞、iPS細胞を用いた毒性評価と創薬研究 難治性血液・免疫疾患由来の疾患特異的iPS細胞を用いた病態解析 (2015)
  • Author(s): 齋藤潤
  • Journal Title: 日本臨牀 Volume: 73 Pages: 423-428
• [Journal Article] iPS細胞を使った血液疾患研究 (2015)
  • Author(s): 齋藤潤、中畑龍俊
  • Journal Title: 病理と臨床 Volume: 33 Pages: 582-586
• [Journal Article] Modeling the early phenotype at the euromuscular junction of spinal muscular atrophy using patient-derived iPSCs. (2015)
  • Author(s): Yoshida, M., Kitaoka, S., Egawa N., Yamane M., Ikeda R., Tsukita K., Amano N., Watanabe A., Morimoto, M., Takahashi J., Hosoi H., Nakahatan, T., Inoue, H.,Saito, Megumu K.
  • Journal Title: Stem Cell Reports Volume: 4 Issue: 4 Pages: 1-8
  • DOI: 10.1016/j.stemcr.2015.02.010
  • Peer Reviewed
• [Journal Article] Pluripotent cell models of Fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors. (2015)
  • Author(s): Suzuki NM, Niwa A, Yabe M, Hira A, Okada C, Amano N, Watanabe A, Watanabe K, Heike T, Takata M, Nakahata T, Saito MK
  • Journal Title: Stem Cells Transl Med Volume: 4 Issue: 4 Pages: 333-338
  • DOI: 10.5966/sctm.2013-0172
  • NAID: 120005980869
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced chondrogenesis of induced pluripotent stem cells from patients with neonatal-onset multisystem inflammatory disease occurs via the caspase 1-independent cAMP/protein kinase A/CREB pathway (2015)
  • Author(s): Yokoyama, K. Ikeya, M. Umeda, K. Oda, H. Nodomi, S. Nasu, A. Matsumoto, Y. Izawa, K. Horigome, K. Kusaka, T. Tanaka, T. Saito, M. K. Yasumi, T. Nishikomori, R. Ohara, O. Nakayama, N. Nakahata, T. Heike, T. Toguchida, J.
  • Journal Title: Arthritis Rheumatol Volume: 67 Issue: 1 Pages: 302-314
  • DOI: 10.1002/art.38912
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 患者由来iPS細胞を用いた疾患モデル作成研究：血液免疫疾患 (2015)
  • Author(s): 齋藤潤
  • Journal Title: 医学のあゆみ Volume: 252 Pages: 899-903
• [Journal Article] 脊髄性筋萎縮症 (2015)
  • Author(s): 吉田路子、斎藤潤
  • Journal Title: 遺伝子医学MOOK Volume: 27 Pages: 66-70
• [Journal Article] Fanconi貧血患者特異的iPS細胞研究の現状と展望 (2015)
  • Author(s): 鈴木直也、斎藤潤
  • Journal Title: 遺伝子医学MOOK Volume: 27 Pages: 120-125
• [Journal Article] 疾患iPS細胞を用いたFanconi貧血の病態解明 (2015)
  • Author(s): 齋藤潤、鈴木直也
  • Journal Title: 血液内科 Volume: 70 Pages: 362-367
• [Journal Article] Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media. (2014)
  • Author(s): Fukuta M, Nakai Y, Kirino K, Nakagawa M, Sekiguchi K, Nagata S, Matsumoto Y, Yamamoto T, Umeda K, Heike T, Okumura N, Koizumi N, Sato T, Nakahata T, Saito M, Otsuka T, Kinoshita S, Ueno M, Ikeya M, Toguchida J.
  • Journal Title: PLOS ONE Volume: 9 Issue: 12 Pages: e112291-e112291
  • DOI: 10.1371/journal.pone.0112291
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 再生医療-iPS細胞の応用 (2014)
  • Author(s): 齋藤潤
  • Journal Title: 日本呼吸器学会雑誌 Volume: 3 Pages: 625-629
• [Journal Article] Somatic NLRP3 mosaicism in Muckle-Wells syndrome. A genetic mechanism shared by different phenotypes of cryopyrin-associated periodic syndromes. (2014)
  • Author(s): Nakagawa K, Kawai T, Umebayashi H, Takei S, Kobayashi N, Yashiro M, Kubota T, Koike R, Akuta N, Shimoyama K, Iwata N, Saito MK, Ohara O, Kambe N, Yasumi T, Izawa K, Kawai T, Heike T, Yagüe J, Nishikomori R, Aróstegui JI et al.
  • Journal Title: Ann Rheum Dis. Volume: in press Issue: 3 Pages: 1-8
  • DOI: 10.1136/annrheumdis-2013-204361
  • Peer Reviewed / Open Access
• [Journal Article] HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis. (2014)
  • Author(s): Morishima T, Watanabe K, Niwa A, Hirai H, Saida S, Tanaka T, Kato I, Umeda K, Hiramatsu H, Saito MK, Matsubara K, Adachi S, Kobayashi M, Nakahata T, Heike T
  • Journal Title: Haematologica Volume: 99(1) Issue: 1 Pages: 19-27
  • DOI: 10.3324/haematol.2013.083873
  • Peer Reviewed / Open Access
• [Journal Article] Robust and highly-efficient differentiation of functional monocytic cells from human pluripotent stem cells under serum- and feeder cell- free conditions. (2013)
  • Author(s): Yanagimachi MD, Niwa A, Tanaka T, Ozaki F, Nishimoto S, Murata Y, Yasumi T, Ito J, Tomida S, Oshima K, Asaka I, Goto H, Heike T, Nakahata T, Saito MK
  • Journal Title: PLoS ONE Volume: 8(4) Issue: 4 Pages: e59243-e59243
  • DOI: 10.1371/journal.pone.0059243
  • NAID: 120005244458
  • Peer Reviewed
• [Journal Article] iPS細胞を用いた難病研究 (2013)
  • Author(s): 齋藤潤
  • Journal Title: アレルギー・免疫 Volume: 20 Pages: 1410-1415
• [Journal Article] 疾患特異的iPS細胞を用いた難治性血液・免疫疾患の病態解析 (2013)
  • Author(s): 齋藤潤
  • Journal Title: Medical Science Digest Volume: 39 Pages: 522-525
• [Presentation] 血液疾患 iPS 細胞モデルと創薬 (2016)
  • Author(s): 齋藤潤
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-17
  • Invited
• [Presentation] iPS 細胞を用いた 自己炎症疾患研究の現状と展望 (2016)
  • Author(s): 齋藤潤
  • Organizer: 第9回自己炎症疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-02-06
  • Invited
• [Presentation] iPS 細胞を用いた血液疾患の疾患モデリング (2016)
  • Author(s): 齋藤潤
  • Organizer: 細胞アッセイ研究会
  • Place of Presentation: 東京
  • Year and Date: 2016-01-19
  • Invited
• [Presentation] iPS 細胞を用いた 血液疾患の創薬に向けた研究 (2015)
  • Author(s): 齋藤潤
  • Organizer: 創薬シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2015-12-14
  • Invited
• [Presentation] iPS細胞による小児免疫疾患の病態解析 (2015)
  • Author(s): 齋藤潤
  • Organizer: 臨床免疫学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-10-22
  • Invited
• [Presentation] iPS細胞を用いた病態解析の試み (2015)
  • Author(s): 齋藤潤
  • Organizer: 小児リウマチ学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-10
  • Invited
• [Presentation] iPS細胞を用いた血液疾患の病態解析 (2015)
  • Author(s): 齋藤潤
  • Organizer: 第26回長崎障害者支援再生医療研究会
  • Place of Presentation: 長崎
  • Year and Date: 2015-09-01
  • Invited
• [Presentation] CAPSのiPS研究について (2015)
  • Author(s): 齋藤潤
  • Organizer: 第3回CAPS勉強会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-25
  • Invited
• [Presentation] CAPS の臨床と疾患特異的 iPS 細胞を用いた病態研究 (2015)
  • Author(s): 齋藤潤
  • Organizer: 第114回日本皮膚科学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-05-29
  • Invited
• [Presentation] 疾患特異的iPS細胞を用いた 血液疾患の病態解析 (2015)
  • Author(s): 齋藤潤
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-03-19
  • Invited
• [Presentation] 再生医療用iPS細胞ストックの ドナーリクルートについて (2014)
  • Author(s): 齋藤潤
  • Organizer: 日本臓器保存生物医学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] 疾患特異的iPS細胞を用いた 免疫疾患の病態解析 (2014)
  • Author(s): 齋藤潤
  • Organizer: 横浜小児先端セミナー
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-12
  • Invited
• [Presentation] 疾患特異的iPS細胞を用いた 免疫疾患の病態解析 (2014)
  • Author(s): 齋藤潤
  • Organizer: 第6回炎症性腸疾患と免疫を語る会
  • Place of Presentation: 横浜
  • Year and Date: 2014-06-26
  • Invited
• [Presentation] 疾患ｉＰＳ細胞を用いた血液・免疫疾患の病態解析 (2014)
  • Author(s): 齋藤潤
  • Organizer: 第5回小児炎症研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-06-21
  • Invited
• [Presentation] 疾患特異的iPS細胞を用いた 免疫疾患の解析について (2014)
  • Author(s): 齋藤潤
  • Organizer: 大阪リウマチカンファレンス
  • Place of Presentation: 大阪
  • Year and Date: 2014-04-19
  • Invited
• [Presentation] iPS細胞研究の現状について
  • Author(s): 齋藤潤
  • Organizer: 日本QA研究会
  • Place of Presentation: 新潟
  • Invited
• [Presentation] 疾患iPS細胞を用いた病態解析と創薬の試み
  • Author(s): 齋藤潤
  • Organizer: 第4回スクリーニング学研究会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 疾患iPS細胞を用いた小児疾患の病態解析
  • Author(s): 齋藤潤
  • Organizer: 京津小児診療最前線セミナー2013
  • Place of Presentation: 京都
  • Invited
• [Presentation] 疾患iPS細胞を用いた血液疾患の病態解析
  • Author(s): 齋藤潤
  • Organizer: 第17回九州小児血液セミナー
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Disease-specific iPS cells derived from patients with hematological and immunological disorders
  • Author(s): Saito MK
  • Organizer: CiRA symposium
  • Place of Presentation: 大阪
  • Invited