新規SWI/SNF複合体の機能喪失に基づくMDS発症機構の解明と治療応用

2021 Fiscal Year Annual Research Report

• Project/Area Number: 20H03717
• Research Institution: Foundation for Biomedical Research and Innovation at Kobe
• Principal Investigator: 井上 大地 公益財団法人神戸医療産業都市推進機構, その他部局等, 研究員(副センター長・部長クラス) (80735746)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 造血幹細胞 / クロマチン / BRD9 / CTCF

Outline of Annual Research Achievements

凍結胚を用いた新動物施設へのマウス移動のため、若干の遅れが見られていたが、2022年5月までに当初予定していたBrd9ノックアウトマウスの造血幹細胞のHiC解析まで完了した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

新動物施設への移動による時間的ロスを最小限に抑え、論文化に向けたデータ取得ができている。

Strategy for Future Research Activity

すでに取得したHiCデータを用いて、BRD9の喪失によるクロマチン3次元構造の変化について、クロマチンリモデリング複合体およびCTCFとの関連性に注目しながら解析を進めていく。また得られた結果を元に造血幹細胞の分化運命制御についてクロマチン構造の観点から考察する。

Research Products

• [Journal Article] MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis (2022)
  • Author(s): Hayashi Yasutaka, Inoue Daichi, Kitamura Toshio et al.
  • Journal Title: Cell Reports Volume: 39 Pages: 110805～110805
  • DOI: 10.1016/j.celrep.2022.110805
  • Peer Reviewed / Open Access
• [Journal Article] Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia. (2022)
  • Author(s): Tanaka Atsushi, Inoue Daichi et al.
  • Journal Title: Blood Volume: 140 Pages: 875～888
  • DOI: 10.1182/blood.2021015325
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysregulated minor intron splicing in cancer (2022)
  • Author(s): Nishimura Koutarou, Yamazaki Hiromi, Zang Weijia, Inoue Daichi
  • Journal Title: Cancer Science Volume: 113 Pages: 2934～2942
  • DOI: 10.1111/cas.15476
  • Peer Reviewed / Open Access
• [Journal Article] Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation (2022)
  • Author(s): Chen Sisi, Inoue Daichi, Abdel-Wahab Omar et al.
  • Journal Title: Cancer Discovery Volume: 12 Pages: 2434～2453
  • DOI: 10.1158/2159-8290.CD-21-1631
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Exploring the mechanistic link between SF3B1 mutation and ring sideroblast formation in myelodysplastic syndrome (2022)
  • Author(s): Ochi Tetsuro, Fujiwara Tohru, Ono Koya, Suzuki Chie, Nikaido Maika, Inoue Daichi, Kato Hiroki, Onodera Koichi, Ichikawa Satoshi, Fukuhara Noriko, Onishi Yasushi, Yokoyama Hisayuki, Nakamura Yukio, Harigae Hideo
  • Journal Title: Scientific Reports Volume: 12 Pages: 14562
  • DOI: 10.1038/s41598-022-18921-2
  • Peer Reviewed / Open Access
• [Presentation] Dual roles of BRD9 in normal and malignant hematopoiesis. (2023)
  • Author(s): Inoue Daichi
  • Organizer: ASH/JSH 2023 Normal/Malignant Hematopoiesis and Novel Therapies for Hematologic Malignancies Symposium
  • Int'l Joint Research / Invited
• [Presentation] ブロモドメインタンパクの転写後制御を介した造血幹細胞運命制御機構 (2022)
  • Author(s): 井上大地
  • Organizer: 第45回日本分子生物学会年会（幕張）
  • Invited
• [Presentation] ブロモドメインタンパクのスプライシング異常がもたらす細胞運命制御 (2022)
  • Author(s): 井上大地
  • Organizer: 第95回日本生化学会大会（名古屋）
  • Invited
• [Presentation] Dysregulated Minor Intron Splicing and Cancer. (2022)
  • Author(s): Inoue Daichi
  • Organizer: 第81回日本癌学会学術総会（横浜）
  • Invited
• [Presentation] Dissecting the mechanisms for cancer development caused by aberrant splicing. (2022)
  • Author(s): Inoue Daichi
  • Organizer: The 12th AACR-JCA Joint Conference
  • Int'l Joint Research / Invited
• [Presentation] Aberrant splicing events lead to altered cell fate of hematopoietic stem cells. (2022)
  • Author(s): Inoue Daichi
  • Organizer: The 19th Stem Cell Research Symposium
  • Int'l Joint Research / Invited