Experimental approach to understand the mechanism mediating epigenome formation in the primate brain by the evolutionary acquisition of non-coding RNAs
| Project/Area Number |
19H03138
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 42030:Animal life science-related
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| Research Institution | Hiroshima University (2020-2021)
Kyushu University (2019) |
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Principal Investigator |
IMAMURA TAKUYA 広島大学, 統合生命科学研究科(理), 教授 (90390682)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2021: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | ノンコーディングRNA / エピゲノム / 霊長類 / 脳 / 動物種差 / ノンコーディングRMA / オルガノイド |
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| Outline of Research at the Start |
脳の形態学的・機能的な違いは遺伝的に98%の相同性を示すヒト・サルでも明らかであり、実験動物として汎用されるマウスも、殆どの遺伝子セットを共通に利用していながら、独特な神経系を獲得している。一方、タンパクになれないノンコーディングRNAセットは種間多様度が極めて高い。本課題では、ノンコーディングRNAを高度に利用し、それにより、霊長類大脳皮質の遺伝子発現制御をげっ歯類細胞に再現することで、マウスのようなモデル実験動物種を異なる動物種の形質理解のために利用できるようにリソース化を目指す。
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| Outline of Final Research Achievements |
In this study, we focused on the regulatory mechanisms that differentiate the gene expression patterns in primate and rodents, that possibly lead to the differential morphology and functions of organs depending on species through epigenetic mechanisms. Utilizing the neural stem cells, we identified a fraction of species specific promoter-associated non-coding RNAs (pancRNA) that can specifically upregulate the partner genes. Among them, most of the human-specific pancRNAs were related to the cell cycle progression, and the mimicking the human type expression in the fetal mouse neural stem cells by in utero electroporation frequently showed the enlargement of the neocortex.
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| Academic Significance and Societal Importance of the Research Achievements |
従来、種を超えて高い相同性を示す分子の振る舞いを指標に、多細胞系の形成と機能化のロジックを解く研究が進められてきた。しかし、獣医学・畜産学領域ではさまざまな動物を取り扱うため、個体や臓器の高度な活用や疾病治療に向けては、種にしたがったロジックの違いをよく理解するための動物生命科学を発展させる必要がある。本研究により、種に固有の臓器形成メカニズムを司るネットワークモジュール群が明らかになりつつあり、今後は動物組織を適応・進化させる原動力を紐解くことで、疾病ゲノムから明らかにする従来型データ解析とは全く異なる礎とし、また、新しい実験動物提供等の応用基盤創出に繋げることが期待できる。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Generation of ovarian follicles from mouse pluripotent stem cells2021
Author(s)
Yoshino Takashi、Suzuki Takahiro、Nagamatsu Go、Yabukami Haruka、Ikegaya Mika、Kishima Mami、Kita Haruka、Imamura Takuya、Nakashima Kinichi、Nishinakamura Ryuichi、Tachibana Makoto、Inoue Miki、Shima Yuichi、Morohashi Ken-ichirou、Hayashi Katsuhiko
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Journal Title
Science
Volume: 373
Issue: 6552
Pages: 282-289
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling2021
Author(s)
Nakashima H, Tsujimura K, Irie K, Imamura T, Trujillo CA, Ishizu M, Uesaka K, Pan M, Noguchi H, Andoh-Noda T, Okano H, Muotri AR, Nakashima K
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Journal Title
Cell Rep
Volume: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Conditional Kisspeptin Neuron-Specific Kiss1 Knockout With Newly Generated Kiss1-floxed and Kiss1-Cre Mice Replicates a Hypogonadal Phenotype of Global Kiss1 Knockout Mice2020
Author(s)
Kana Ikegami, Teppei Goto, Sho Nakamura, Youki Watanabe, Arisa Sugimoto, Sutisa Majarune, Kei Horihata, Mayuko Nagae, Junko Tomikawa, Takuya Imamura, Makoto Sanbo, Masumi Hirabayashi, Naoko Inoue, Kei-Ichiro Maeda, Hiroko Tsukamura, Yoshihisa Uenoyama
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Journal Title
J Reprod Dev.
Volume: in press
Issue: 4
Pages: 359-367
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inducible Kiss1 knockdown in the hypothalamic arcuate nucleus suppressed pulsatile secretion of luteinizing hormone in male mice2020
Author(s)
Shiori Minabe, Sho Nakamura, Eri Fukushima, Marimo Sato, Kana Ikegami, Teppei Goto, Makoto Sanbo, Masumi Hirabayashi, Junko Tomikawa, Takuya Imamura, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura, Kei-Ichiro Maeda, Fuko Matsuda
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Journal Title
Journal of Reproduction and Development
Volume: Epub
Issue: 4
Pages: 369-375
DOI
NAID
Related Report
Peer Reviewed / Open Access
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