The effects of ionizing radiation on early development stage of the fertilized egg

• Project/Area Number: 18K18196
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Hiroshima University
• Principal Investigator: Kanai Akinori 広島大学, 原爆放射線医科学研究所, 助教 (60549567)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 放射線 / 受精卵 / 次世代シーケンサー / バイオインフォマティクス

Outline of Final Research Achievements

In this study, we analyzed the effects of low-dose radiation on early implantation embryos using fertilized mouse eggs. In the case of mouse fertilized eggs, the greatest decrease in development was observed at 5 hours after fertilization, confirming the high sensitivity to radiation. When the fertilized eggs were irradiated with 0.1 Gy, only developmental arrest at the morula stage was observed, but when the eggs were irradiated with 1 Gy, two stages of developmental arrest were observed: one at the 1-4 cell stage and the other at the morula stage. Transcriptome analysis of the morula embryos suggested that the same mechanism of developmental arrest at the morula stage was observed at 0.1 and 1 Gy.

Academic Significance and Societal Importance of the Research Achievements

妊娠期における放射線被曝影響は、胎芽・胎児の発育期によって著しく異なることが明らかにされているが、妊娠期における低線量放射線が与える影響に関しては未だ不明な点が多い。本研究によって、マウス受精卵は媒精後5時間の段階で放射線の影響を最も受けることを確認し、線量の違いによって発生停止段階が異なることも確認した。これらのことはヒト受精卵においても同様に放射線の影響を受ける事が予想される。
また、受精卵への影響の分子機構を調べるために遺伝子解析も行うことで受精卵の発生停止に影響する候補のひとつとしてTrim43遺伝子群を見出し、今後詳細な解析を進めるつもりである。

Research Products

• [Journal Article] Overexpression of Hmga2 activates Igf2bp2 and remodels transcriptional program of Tet2-deficient stem cells in myeloid transformation (2021)
  • Author(s): Bai Jie、Yokomizo-Nakano Takako、Kubota Sho、Sun Yuqi、Kanai Akinori、Iimori Mihoko、Harada Hironori、Iwama Atsushi、Sashida Goro
  • Journal Title: Oncogene Volume: 40 Issue: 8 Pages: 1531-1541
  • DOI: 10.1038/s41388-020-01629-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multi-organ failure with abnormal receptor metabolism in mice mimicking Samd9/9L syndromes (2021)
  • Author(s): Nagamachi A, Kanai A, Nakamura M, Okuda H, Yokoyama A, Shinriki S, Matsui H, Inaba T.
  • Journal Title: J Clin Invest Volume: 131 Issue: 4 Pages: 1-16
  • DOI: 10.1172/jci140147
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] UTX maintains functional integrity of murine hematopoietic system by globally regulating aging-associated genes. (2021)
  • Author(s): Sera Y; Nakata Y; Ueda T; Yamasaki N; Koide S; Kobayashi H; Ikeda KI; Kobatake K; Iwasaki M; Oda H; Wolff L; Kanai A; Nagamachi A; Inaba T; Sotomaru Y; Ichinohe T; Koizumi M; Miyakawa Y; Honda ZI; Iwama A; Suda T; Takubo K; Honda H
  • Journal Title: Blood. Volume: 137 Issue: 7 Pages: 908-922
  • DOI: 10.1182/blood.2019001044
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Activation of CpG-Rich Promoters Mediated by MLL Drives MOZ-Rearranged Leukemia (2020)
  • Author(s): Miyamoto Ryo、Okuda Hiroshi、Kanai Akinori、Takahashi Satoshi、Kawamura Takeshi、Matsui Hirotaka、Kitamura Toshio、Kitabayashi Issay、Inaba Toshiya、Yokoyama Akihiko
  • Journal Title: Cell Reports Volume: 32 Issue: 13 Pages: 108200-108200
  • DOI: 10.1016/j.celrep.2020.108200
  • Peer Reviewed / Open Access
• [Journal Article] HHEX promotes myeloid transformation in cooperation with mutant ASXL1. (2020)
  • Author(s): Takeda R, Asada S, Park SJ, Yokoyama A, Becker H, Kanai A, Visconte V, Hershberger C, Hayashi Y, Yonezawa T, Tamura M, Fukushima T, Tanaka Y, Fukuyama T, Matsumoto A, Yamasaki S, Nakai K, Yamazaki S, Inaba T, Shibata T, Inoue D, Honda H, Goyama S, Maciejewski J, Kitamura T.
  • Journal Title: Blood Volume: 136 Pages: 1670-1684
  • DOI: 10.1182/blood.2019004613
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of novel methylation markers in HPV-associated oropharyngeal cancer: genome-wide discovery, tissue verification and validation testing in ctDNA. (2020)
  • Author(s): Misawa K, Imai A, Matsui H, Kanai A, Misawa Y, Mochizuki D, Mima M, Yamada S, Kurokawa T, Nakagawa T and Mineta H
  • Journal Title: Oncogene Volume: 39(24) Issue: 24 Pages: 4741-4755
  • DOI: 10.1038/s41388-020-1327-z
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of RUNX3 Represses RUNX1 to Drive Transformation of Myelodysplastic Syndrome (2020)
  • Author(s): Yokomizo-Nakano Takako、Kubota Sho、Bai Jie、Hamashima Ai、Morii Mariko、Sun Yuqi、Katagiri Seiichiro、Iimori Mihoko、Kanai Akinori、Tanaka Daiki、Oshima Motohiko、Harada Yuka、Ohyashiki Kazuma、Iwama Atsushi、Harada Hironori、Osato Motomi、Sashida Goro
  • Journal Title: Cancer Research Volume: 80 Issue: 12 Pages: 2523-2536
  • DOI: 10.1158/0008-5472.can-19-3167
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of a Novel Murine Colon Carcinoma Subline with High-Metastatic Activity Established by In Vivo Selection Method (2020)
  • Author(s): Ma Liqiu、Sakamoto Yoshimitsu、Kanai Akinori、Otsuka Hiromi、Takahashi Akihisa、Kakimi Kazuhiro、Imai Takashi、Shimokawa Takashi
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 8 Pages: 2829-2829
  • DOI: 10.3390/ijms21082829
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A. (2020)
  • Author(s): Kazumi Shimamoto, Keiji Tanimoto*, Takahiro Fukazawa, Hideaki Nakamura, Akinori Kanai, Hidemasa Bono, Hiromasa Ono, Hidetaka Eguchi, Nobuyuki Hirohashi
  • Journal Title: Carcinogenesis Volume: inpress Issue: 9 Pages: 1184-1194
  • DOI: 10.1093/carcin/bgaa010
  • Peer Reviewed
• [Journal Article] Kdm6a Deficiency Activates Inflammatory Pathways, Promotes M2 Macrophage Polarization, and Causes Bladder Cancer in Cooperation with p53 Dysfunction (2020)
  • Author(s): Kobatake Kohei et al., Honda Zen-ichiro et al. and Honda Hiroaki
  • Journal Title: Clinical Cancer Research Volume: 26 Issue: 8 Pages: 2065-2079
  • DOI: 10.1158/1078-0432.ccr-19-2230
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lineage-specific RUNX2 super-enhancer activates MYC via a chromosomal translocation and promotes the development of blastic plasmacytoid dendritic cell neoplasm (2019)
  • Author(s): Kubota S, Tokunaga K, Umezu T, Yokomizo-Nakano T, Oshima M, Tan KT, Yang H, Kanai A. Iwanaga E, Asou N, Maeda T, Nakagata N. Ito T, Iwama A. Ohyashiki K, Osato M, Sashida G.
  • Journal Title: Nat Commun Volume: 10 Issue: 1 Pages: 1653-1653
  • DOI: 10.1038/s41467-019-09710-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A cell-based high-throughput screening method to directly examine transthyretin amyloid fibril formation at neutral pH (2019)
  • Author(s): Ueda Mitsuharu、Okada Masamitsu、Mizuguchi Mineyuki、et al.
  • Journal Title: Journal of Biological Chemistry Volume: 294 Issue: 29 Pages: 11259-11275
  • DOI: 10.1074/jbc.ra119.007851
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clonal hematopoiesis by SLIT1-mutated hematopoietic stem cells due to a breakdown of the autocrine loop involving Slit1 in acquired aplastic anemia (2019)
  • Author(s): Hosokawa K, Mizumaki H, Elbadry M, Saito C, Espinoza JL, An DTT, Katagiri T, Harashima A, Kikuchi A, Kanai A, Matsui H, Inaba T, Taniwaki M, Yamamoto Y, Nakao S
  • Journal Title: Leukemia Volume: 33 Issue: 11 Pages: 2732-2766
  • DOI: 10.1038/s41375-019-0510-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High fat diet triggers a reduction in body fat mass in female mice deficient for Utx demethylase (2019)
  • Author(s): Ota K, Komuro A, Amano H, Kanai A, Ge K, Ueda T, Okada H
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 10036-10036
  • DOI: 10.1038/s41598-019-46445-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intense Expression of EGFR L858R Characterizes the Micropapillary Component and L858R Is Associated with the Risk of Recurrence in pN0M0 Lung Adenocarcinoma with the Micropapillary Component (2019)
  • Author(s): Kishi Naoto、Ito Masaoki、Miyata Yoshihiro、Kanai Akinori、Handa Yoshinori、Tsutani Yasuhiro、Kushitani Kei、Takeshima Yukio、Okada Morihito
  • Journal Title: Annals of Surgical Oncology Volume: 27 Issue: 3 Pages: 945-955
  • DOI: 10.1245/s10434-019-07854-2
  • Peer Reviewed
• [Journal Article] BRD4-Regulated Molecular Targets in Mantle Cell Lymphoma: Insights into Targeted Therapeutic Approach (2019)
  • Author(s): TSUKAMOTO TAKU、NAKAHATA SHINGO、SATO RYUICHI、KANAI AKINORI、NAKANO MASAKAZU、CHINEN YOSHIAKI、MAEGAWA-MATSUI SAORI、MATSUMURA-KIMOTO YAYOI、TAKIMOTO-SHIMOMURA TOMOKO、MIZUNO YOSHIMI、KUWAHARA-OTA SAEKO、KAWAJI YUKA、TANIWAKI MASAFUMI、INABA TOSHIYA、TASHIRO KEI、MORISHITA KAZUHIRO、KURODA JUNYA
  • Journal Title: Cancer Genomics - Proteomics Volume: 17 Issue: 1 Pages: 77-89
  • DOI: 10.21873/cgp.20169
  • Peer Reviewed / Open Access
• [Journal Article] A novel ASXL1?OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies (2018)
  • Author(s): Inoue D, Fujino T, Sheridan P, Zhang YZ, Nagase R, Horikawa S, Li Z, Matsui H, Kanai A, Saika M, Yamaguchi R, Kozuka-Hata H, Kawabata KC, Yokoyama A, Goyama S, Inaba T, Imoto S, Miyano S, Xu M, Yang FC, Oyama M, Kitamura T.
  • Journal Title: Leukemia Volume: 印刷中 Issue: 6 Pages: 1327-1337
  • DOI: 10.1038/s41375-018-0083-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation (2018)
  • Author(s): Nagase R, Inoue D, Pastore A, Fujino T, Hou HA, Yamasaki N, Goyama S, Saika M, Kanai A, Sera Y, Horikawa S, Ota Y, Asada S, Hayashi Y, Kawabata KC, Takeda R, Tien HF, Honda H, Abdel-Wahab O, Kitamura T.
  • Journal Title: The Journal of Experimental Medicine Volume: 印刷中 Issue: 6 Pages: 1729-1747
  • DOI: 10.1084/jem.20171151
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ezh2 loss propagates hypermethylation at T cell differentiation?regulating genes to promote leukemic transformation (2018)
  • Author(s): Wang Changshan、Oshima Motohiko、Sato Daisuke、Matsui Hirotaka、Kubota Sho、Aoyama Kazumasa、Nakajima-Takagi Yaeko、Koide Shuhei、Matsubayashi Jun、Mochizuki-Kashio Makiko、Nakano-Yokomizo Takako、Bai Jie、Nagao Toshitaka、Kanai Akinori、Iwama Atsushi、Sashida Goro
  • Journal Title: Journal of Clinical Investigation Volume: 128 Issue: 9 Pages: 3872-3886
  • DOI: 10.1172/jci94645
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Effect of ionizing radiation on the development of early mouse embryos. (2020)
  • Author(s): Akinori Kanai, Natsumi Shimizu, Akiko Nagamachi, Hidehiko Kawai, Toshiya Inaba
  • Organizer: 第63回 放射線影響学会
• [Presentation] Effect of ionizing radiation on the development of early mouse embryos (2019)
  • Author(s): Akinori Kanai, Natsumi Shimizu, Akiko Nagamachi, Hidehiko Kawai, Toshiya Inaba
  • Organizer: 第62回 放射線影響学会
• [Presentation] 低線量放射線が着床前期胚に与える影響の解析 (2019)
  • Author(s): 金井昭教, 清水なつみ, 長町安希子, 河合秀彦, 稲葉俊哉
  • Organizer: 第42回 分子生物学会
• [Presentation] Target genes of DNA demethylating agents for improving anemia of MDS (2018)
  • Author(s): Akinori Kanai
  • Organizer: 第80回日本血液学会学術集会
• [Presentation] 次世代シーケンサを用いた低線量放射線影響研究 (2018)
  • Author(s): 金井 昭教
  • Organizer: 日本放射線影響学会第61回大会
• [Presentation] Target genes of DNA demethylating agents for improving anemia of MDS (2018)
  • Author(s): Akinori Kanai
  • Organizer: 第41回日本分子生物学会年会