Induction of midbrain-like organoids from human pluripotent stem cells
Project/Area Number |
19K21306
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Project/Area Number (Other) |
18H06202 (2018)
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund (2019) Single-year Grants (2018) |
Review Section |
0902:General internal medicine and related fields
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Research Institution | Nara Medical University |
Principal Investigator |
NANAURA HITOKI 奈良県立医科大学, 医学部附属病院, 研究員 (00827909)
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Project Period (FY) |
2018-08-24 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 脳オルガノイド / 神経細胞 / ドパミン / 中脳 / パーキンソン病 |
Outline of Research at the Start |
ヒト中脳の黒質にはドパミン作動性神経細胞が数多く存在し、ドパミン作動性神経細胞の喪失によってパーキンソン病が生じることは広く知られているが、そのメカニズムは未解明な点が多い。ヒト中脳と類似した構造を持つ臓器様組織(ヒト中脳オルガノイド)を試験管内で作製することができれば、これを用いてパーキンソン病の病因解明や治療法開発を、試験管内で解明することが可能となる。またヒト中脳オルガノイド内部に存在するドパミン作動性神経細胞を用いて、パーキンソン病患者に対する細胞補充療法を行うことも可能となる。本研究は、ドパミン作動性神経細胞を有するヒト中脳オルガノイドを短期間で作製する手法の確立を目的とする。
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Outline of Final Research Achievements |
Brain organoids derived from human pluripotent stem cells recapitulate the course of human brain development, and they seem to be useful for medical research on central nervous system disorders such as Parkinson disease. There are few reports of brain organoids mimicking the structure of midbrain. In this study, we aim to develop a new method to induce midbrain-like organoids. Brain organoids were generated at one month, and immunohistochemistry and quantitative polymerase chain reaction confirmed the gene expression of dopaminergic neurons, such as thyrosin hydroxylase. RNA-seq analysis also revealed that the brain organoids contained cell populations like that of a human brainstem. Therefore, our brain organoids might be a useful model of the brainstem.
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Academic Significance and Societal Importance of the Research Achievements |
これまでのヒト脳オルガノイド樹立プロトコルは、大脳皮質構造の再現を目的とするものが多く、中脳など脳幹部の構造を再現可能な手法は限られていた。本研究により、中脳を含めた脳幹部を模倣した脳オルガノイドを短期間で作製する手法を確立した。今後本手法は、パーキンソン病を含めた中枢神経疾患の病因解明や、治療薬剤のスクリーニングなどに有用なモデルとなると考えられる。
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] Brainstem organoids from human pluripotent stem cells2020
Author(s)
Nobuyuki Eura, Takeshi K. Matsui, Joachim Luginbuhl, Masaya Matsubayashi, Hitoki Nanaura, Tomo Shiota, Kaoru Kinugawa, Naohiko Iguchi, Takao Kiriyama, Canbin Zheng, Tsukasa Kouno, Yan Jun Lan, Pornparn Kongpracha, Pattama Wiriyasermkul, Yoshihiko M. Sakaguchi, Riko Nagata, Tomoya Komeda, Naritaka Morikawa, et al.
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Journal Title
Frontiers in Neuroscience
Volume: -
Pages: 00538-00538
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] ATR inhibition enhances 5-fluorouracil sensitivity independent of non-homologous end-joining and homologous recombination repair pathway2020
Author(s)
Ito SS, Nakagawa Y, Matsubayashi M, Sakaguchi YM, Kobashigawa S, Matsui TK, Nanaura H, Nakanishi M, Kitayoshi F, Kikuchi S, Kajihara A, Tamaki S, Sugie K, Kashino G, Takahashi A, Hasegawa M, Mori E
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Journal Title
DOI
Related Report
Open Access
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[Journal Article] Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target Kapβ2 and dysregulate phase separation of low-complexity domains.2019
Author(s)
Nanaura H, Kawamukai H, Fujiwara A, Uehara T, Nakanishi M, Shiota T, Hibino M, Aiba Y, Wiriyasermkul P, Kikuchi S, Nagata R, Matsubayashi M, Nagamori S, Shoji O, Ishimori K, Matsumura H, Sugie K, Saio T*, Yoshizawa T*, Mori E
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Journal Title
DOI
Related Report
Open Access
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[Journal Article] Human URAT1/SLC22A12 gene promoter is regulated by 27-hydroxycholesterol through estrogen response elements2019
Author(s)
Matsubayashi M, Sakaguchi YM, Sahara Y, Nanaura H, Kikuchi S, Ashari A, Bui L, Kobashigawa S, Nakanishi M, Nagata R, Matsui TK, Kashino G, Hasegawa M, Takasawa S, Eriguchi M, Tsuruya K, Nagamori S, Sugie K, Nakagawa T, Takasato M, Umetani M, Mori E
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Journal Title
DOI
Related Report
Open Access / Int'l Joint Research
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[Journal Article] Proteolytic Cleavage by Matriptase Exacerbating Kidney Injury: a Novel Therapeutic Target.2019
Author(s)
Ozawa S, Matsubayashi M, Nanaura H, Yanagita M, Mori K, Asanuma K, Kajiwara N, Hayashi K, Ohashi H, Kasahara M, Yokoi H, Kataoka H, Mori E, Nakagawa T
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Journal Title
DOI
Related Report
Open Access
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