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Elucidation of oocyte molecular mechanism on imprinted X chromosome inactivation enabling a sequential development

Research Project

Project/Area Number 17H01588
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Akutsu Hidenori  国立研究開発法人国立成育医療研究センター, 生殖医療研究部, 部長 (50347225)

Co-Investigator(Kenkyū-buntansha) 中林 一彦  国立研究開発法人国立成育医療研究センター, 周産期病態研究部, 室長 (10415557)
佐渡 敬  近畿大学, 農学部, 教授 (70321601)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥43,030,000 (Direct Cost: ¥33,100,000、Indirect Cost: ¥9,930,000)
Fiscal Year 2019: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2018: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
Fiscal Year 2017: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
KeywordsXist / Oct4 / 初期胚 / 着床 / クロマチン / X染色体 / X染色体不活化 / 胎盤発生 / DNAメチル化 / ヒストン修飾 / 生殖医学 / 受精卵 / 不育症 / 女性医学
Outline of Final Research Achievements

During oocyte maturation, the chromatin is condensed, but after fertilization, the chromatin becomes asymmetric condensing. At the early blastocyst stage, each allylic chromatin relaxes and becomes "Neutral" (chromatin initialization). Subsequently, it has been shown that although placental development takes the form of asymmetric chromatin, random inactivation of the X chromosome occurs in ontogenetic systems under the condensation of random chromatin of both sexes during the peri-implantation periods. Oct4 gene, a pluripotent factor, is responsible for controlling the condensation and relaxation of nuclear chromatin that controls X-chromosome inactivation, and the OCT4 protein acts as a chromatin opener that leads to a relaxed state from chromatin condensation, indicating that the spatiotemporal control of OCT4 is associated with totipotency.

Academic Significance and Societal Importance of the Research Achievements

X染色体不活化は、卵子、初期胚の細胞内動態が胎盤発生と成体健康状態・疾患へ明確に影響するバイオシステムとして研究できる唯一の発生モデルである。着床周辺期までに決定するX染色体不活化分子制御機構を明らかにすることは女性の細胞基本動態を理解することで多領域にわたる女性医学の進展に大きく貢献するものである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (30 results)

All 2020 2019 2018 2017

All Journal Article (22 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 22 results,  Open Access: 18 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 8 results)

  • [Journal Article] Transcriptomic features of trophoblast lineage cells derived from human induced pluripotent stem cells treated with BMP 42020

    • Author(s)
      Tsuchida Nanae、Kojima Junya、Fukuda Atsushi、Oda Mayumi、Kawasaki Tomoyuki、Ito Hiroe、Kuji Naoaki、Isaka Keiichi、Nishi Hirotaka、Umezawa Akihiro、Akutsu Hidenori
    • Journal Title

      Placenta

      Volume: 89 Pages: 20-32

    • DOI

      10.1016/j.placenta.2019.10.006

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epitranscriptomic profiling in human placenta: N6‐methyladenosine modification at the 5′‐untranslated region is related to fetal growth and preeclampsia2020

    • Author(s)
      Taniguchi Kosuke、Kawai Tomoko、Kitawaki Jo、Tomikawa Junko、Nakabayashi Kazuhiko、Okamura Kohji、Sago Haruhiko、Hata Kenichiro
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 1 Pages: 494-512

    • DOI

      10.1096/fj.201900619rr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zscan5b Deficiency Impairs DNA Damage Response and Causes Chromosomal Aberrations during Mitosis.2019

    • Author(s)
      Ogawa S, Yamada M, Nakamura A, Sugawara T, Nakamura A, Miyajima S, Harada Y, Ooka R, Okawa R, Miyauchi J, Tsumura H, Yoshimura Y, Miyado K, Akutsu H, Tanaka M, Umezawa A, Hamatani T.
    • Journal Title

      Stem Cell Reports

      Volume: 12 Issue: 6 Pages: 1366-1379

    • DOI

      10.1016/j.stemcr.2019.05.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aneuploid rescue precedes X-chromosome inactivation and increases the incidence of its skewness by reducing the size of the embryonic progenitor cell pool.2019

    • Author(s)
      Yoshida T, Miyado M, Mikami M, Suzuki E, Kinjo K, Matsubara K, Ogata T, Akutsu H, Kagami M and Fukami M.
    • Journal Title

      Human Reproduction

      Volume: 34 Issue: 9 Pages: 1762-1769

    • DOI

      10.1093/humrep/dez117

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice2019

    • Author(s)
      Ito C, Akutsu H, Yao R, Yoshida K, Yamatoya K, Mutoh T, Makino T, Aoyama K, Ishikawa H, Kunimoto K, Tsukita S, Noda T, Kikkawa M, Toshimori K.
    • Journal Title

      Sci Rep.

      Volume: 9 Issue: 1 Pages: 14249-14249

    • DOI

      10.1038/s41598-019-50516-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imprinted X‐chromosome inactivation impacts primitive endoderm differentiation in mouse blastocysts2019

    • Author(s)
      Fukuda Atsushi、Motosugi Nami、Ando Mikiko、Kimura Minoru、Umezawa Akihiro、Akutsu Hidenori
    • Journal Title

      FEBS Letters

      Volume: 594 Issue: 5 Pages: 913-923

    • DOI

      10.1002/1873-3468.13676

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enhancement of Cellular Adhesion and Proliferation in Human Mesenchymal Stromal Cells by the Direct Addition of Recombinant Collagen I Peptide to the Culture Medium2019

    • Author(s)
      Muraya Koji、Kawasaki Tomoyuki、Yamamoto Takeshi、Akutsu Hidenori
    • Journal Title

      BioResearch Open Access

      Volume: 8 Issue: 1 Pages: 210-218

    • DOI

      10.1089/biores.2019.0012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exploring trophoblast-specific Tead4 enhancers through chromatin conformation capture assays followed by functional screening2019

    • Author(s)
      Tomikawa Junko、Takada Shuji、Okamura Kohji、Terao Miho、Ogata-Kawata Hiroko、Akutsu Hidenori、Tanaka Satoshi、Hata Kenichiro、Nakabayashi Kazuhiko
    • Journal Title

      Nucleic Acids Research

      Volume: 48 Issue: 1 Pages: 278-289

    • DOI

      10.1093/nar/gkz1034

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolution of imprinting via lineage-specific insertion of retroviral promoters2019

    • Author(s)
      Bogutz Aaron B.、Brind’Amour Julie、Kobayashi Hisato、Jensen Kristoffer N.、Nakabayashi Kazuhiko、Imai Hiroo、Lorincz Matthew C.、Lefebvre Louis
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 5674-5674

    • DOI

      10.1038/s41467-019-13662-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Amplicon Sequencing-Based Noninvasive Fetal Genotyping for RHD-Positive D Antigen-Negative Alleles2019

    • Author(s)
      Takahashi Ken、Migita Ohsuke、Sasaki Aiko、Nasu Michiko、Kawashima Akihiro、Sekizawa Akihiko、Sato Taisuke、Ito Yuki、Sago Haruhiko、Okamoto Aikou、Nakabayashi Kazuhiko、Hata Kenichiro
    • Journal Title

      Clinical Chemistry

      Volume: 65 Issue: 10 Pages: 1307-1316

    • DOI

      10.1373/clinchem.2019.307074

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide single nucleotide polymorphism array analysis unveils the origin of heterozygous androgenetic complete moles2019

    • Author(s)
      Usui Hirokazu、Nakabayashi Kazuhiko、Maehara Kayoko、Hata Kenichiro、Shozu Makio
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 12542-12542

    • DOI

      10.1038/s41598-019-49047-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Placenta-specific epimutation at H19-DMR among common pregnancy complications: its frequency and effect on the expression patterns of H19 and IGF22019

    • Author(s)
      Yamaguchi Yuko、Tayama Chiharu、Tomikawa Junko、Akaishi Rina、Kamura Hiromi、Matsuoka Kentaro、Wake Norio、Minakami Hisanori、Kato Kiyoko、Yamada Takahiro、Nakabayashi Kazuhiko、Hata Kenichiro
    • Journal Title

      Clinical Epigenetics

      Volume: 11 Issue: 1 Pages: 113-113

    • DOI

      10.1186/s13148-019-0712-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR12019

    • Author(s)
      Osumi Tomoo、Watanabe Akihiro、Okamura Kohji、Nakabayashi Kazuhiko、Yoshida Masanori、Tsujimoto Shin‐ichi、Uchiyama Meri、Takahashi Hiroyuki、Tomizawa Daisuke、Hata Kenichiro、Kiyokawa Nobutaka、Kato Motohiro
    • Journal Title

      Genes, Chromosomes and Cancer

      Volume: 58 Issue: 11 Pages: 820-823

    • DOI

      10.1002/gcc.22791

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Temple Syndrome in a Patient With Variably Methylated CpGs at the Primary MEG3/DLK1:IG-DMR and Severely Hypomethylated CpGs at the Secondary MEG3:TSS-DMR2019

    • Author(s)
      Kagami M, Yanagisawa A, Ota M, Matsuoka K, Nakamura A, Matsubara K, Nakabayashi K, Takada S, Fukami M, Ogata T.
    • Journal Title

      Clinical Epigenetics

      Volume: 11 Issue: 1 Pages: 41-41

    • DOI

      10.1186/s13148-019-0640-2

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autonomous trisomic rescue of Down syndrome cells2019

    • Author(s)
      Inoue Momoko、Kajiwara Kazuhiro、Yamaguchi Ayumi、Kiyono Tohru、Samura Osamu、Akutsu Hidenori、Sago Haruhiko、Okamoto Aikou、Umezawa Akihiro
    • Journal Title

      Laboratory Investigation

      Volume: Feb 13 Issue: 6 Pages: 1-12

    • DOI

      10.1038/s41374-019-0230-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Manipulation of Xist Imprinting in Mouse Preimplantation Embryos2018

    • Author(s)
      Fukuda Atsushi、Umezawa Akihiro、Akutsu Hidenori
    • Journal Title

      Methods in Molecular Biology

      Volume: 1861 Pages: 47-53

    • DOI

      10.1007/978-1-4939-8766-5_4

    • ISBN
      9781493987658, 9781493987665
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Epigenetic-scale comparison of human iPSCs generated by retrovirus, Sendai virus or episomal vectors2018

    • Author(s)
      Nishino Koichiro、Arai Yoshikazu、Takasawa Ken、Toyoda Masashi、Yamazaki-Inoue Mayu、Sugawara Tohru、Akutsu Hidenori、Nishimura Ken、Ohtaka Manami、Nakanishi Mahito、Umezawa Akihiro
    • Journal Title

      Regenerative Therapy

      Volume: 9 Pages: 71-78

    • DOI

      10.1016/j.reth.2018.08.002

    • NAID

      120007128469

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Reciprocal changes of H3K27ac and H3K27me3 at the promoter regions of the critical genes for endometrial decidualization2018

    • Author(s)
      Katoh Noriko、Kuroda Keiji、Tomikawa Junko、Ogata-Kawata Hiroko、Ozaki Rie、Ochiai Asako、Kitade Mari、Takeda Satoru、Nakabayashi Kazuhiko、Hata Kenichiro
    • Journal Title

      Epigenomics

      Volume: 10 Issue: 9 Pages: 1243-1257

    • DOI

      10.2217/epi-2018-0006

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characterization of parent-of-origin methylation using the Illumina Infinium MethylationEPIC array platform2018

    • Author(s)
      Hernandez Mora Jose R、Tayama Chiharu、S?nchez-Delgado Marta、Monteagudo-S?nchez Ana、Hata Kenichiro、Ogata Tsutomu、Medrano Jose、Poo-Llanillo Maria E、Sim?n Carlos、Moran Sebastian、Esteller Manel、Tenorio Jair、Lapunzina Pablo、Kagami Masayo、Monk David、Nakabayashi Kazuhiko
    • Journal Title

      Epigenomics

      Volume: 10 Issue: 7 Pages: 941-954

    • DOI

      10.2217/epi-2017-0172

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Elucidation of the developmental mechanism of ovarian mature cystic teratomas using B allele-frequency plots of single nucleotide polymorphism array data2018

    • Author(s)
      Usui Hirokazu、Nakabayashi Kazuhiko、Kaku Hiroshi、Maehara Kayoko、Hata Kenichiro、Shozu Makio
    • Journal Title

      Genes, Chromosomes and Cancer

      Volume: 57 Issue: 8 Pages: 409-419

    • DOI

      10.1002/gcc.1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The serine 106 residue within the N-terminal transactivation domain is crucial for Oct4 function in mice2017

    • Author(s)
      Mitani A, Fukuda A, Miyashita T, Umezawa A, Akutsu H
    • Journal Title

      zygote

      Volume: 25 Issue: 2 Pages: 197-204

    • DOI

      10.1017/s0967199417000053

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] DNA hypermethylation enhanced telomerase reverse transcriptase expression in human-induced pluripotent stem cells.2017

    • Author(s)
      Takasawa K, Arai Y, Yamazaki-Inoue M, Toyoda M, Akutsu H, Umezawa A, Nishino K.
    • Journal Title

      Human Cell

      Volume: 31 Issue: 1 Pages: 78-86

    • DOI

      10.1007/s13577-017-0190-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ゲノム編集技術を応用したヒト受精胚研究について2019

    • Author(s)
      阿久津英憲
    • Organizer
      第122回日本小児科学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ゲノム編集技術を応用したヒト受精胚研究について2019

    • Author(s)
      阿久津英憲
    • Organizer
      第37回日本受精着床学会学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ゲノム編集の治療応用と倫理的課題2019

    • Author(s)
      阿久津英憲
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒト受精卵とゲノム編集研究:臨床利用は有りか無しか2019

    • Author(s)
      阿久津英憲
    • Organizer
      第 64 回日本生殖医学学会学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ゲノム編集技術による研究と応用の課題2019

    • Author(s)
      阿久津英憲
    • Organizer
      第31回日本生命倫理学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ゲノム編集技術のヒト受精卵への応用~ARTに携わる人が考えなければならないこととは~2019

    • Author(s)
      阿久津英憲
    • Organizer
      第25回日本臨床エンブリオロジスト学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヒト ES細胞の臨床応用2018

    • Author(s)
      阿久津英憲
    • Organizer
      第59回日本卵子学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regulatory Actions for Researches Using Genome Editing Technology on Human Embryos in Japan2018

    • Author(s)
      Hidenori Akutsu
    • Organizer
      Second International Summit on Human Genome Editing
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2017-04-28   Modified: 2021-02-19  

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