Generation of hypothalamic neural stem cells in vitro from human pluripotent stem cells
Project/Area Number |
20K08859
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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Research Institution | Nagoya University |
Principal Investigator |
Suga Hidetaka 名古屋大学, 医学系研究科, 准教授 (20569818)
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Co-Investigator(Kenkyū-buntansha) |
有馬 寛 名古屋大学, 医学系研究科, 教授 (50422770)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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Keywords | ヒト多能性幹細胞 / 視床下部 / 幹細胞 / 神経幹細胞 |
Outline of Research at the Start |
ヒト多能性幹細胞(ES細胞、iPS細胞)から視床下部神経幹細胞への分化誘導法を確立し、誘導した細胞が神経幹細胞として機能を果たすことを示す。 視床下部神経組織は再生能力が低く、一旦傷つくと回復は難しい。我々はマウスES細胞から視床下部神経を分化させ、その中に増殖能と分化能とを併せ持った細胞、すなわち神経幹細胞が存在することを証明し、単離することに成功した。一方、ヒトでは生体から視床下部組織を採取することが難しく、神経幹細胞の研究は進んでいない。本研究ではヒトES細胞・iPS細胞を利用し、vitroでの分化技術と合わせ、ヒトの視床下部における神経幹細胞の存在に迫る。
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Outline of Final Research Achievements |
In this study, we induced human hypothalamic neural tissue organoids using human ESCs (hESCs), attempted to fractionate hypothalamic neural stem cell-like cells from the organoids, and examined whether these fractionated cells have tissue stem cell properties. We focused on RAX and differentiated RAX::VENUS knock-in hESCs into hypothalamic organoids and sorted RAX-positive cells from mature organoids. The isolated RAX-positive cells formed neurospheres and exhibited self-renewal and multipotency. Neurogenesis was observed when neurospheres were transplanted into the mouse hypothalamus. We isolated RAX-positive hypothalamic neural stem cell-like cells from wild-type human ES organoids. This is the first study to differentiate human hypothalamic neural stem cell-like cells from pluripotent stem cells.
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Academic Significance and Societal Importance of the Research Achievements |
ヒトES細胞から視床下部神経幹細胞の性質を持つ細胞を作製する基盤技術ができたと考えられる。視床下部は体の恒常性を保つ重要な器官だがひとたび傷つくと回復しない。今後視床下部障害を来した患者さんに対する再生医療実現のための技術となることが期待される。またマウスの視床下部神経幹細胞から分泌されるエクソソームは抗加齢作用を持つと報告されており、加齢に関する研究にも役立つと考えられる。
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Report
(4 results)
Research Products
(44 results)
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[Journal Article] Generation of hypothalamic neural stem cell-like cells in vitro from human pluripotent stem cells.2023
Author(s)
Miwata T, Suga H*, Kawaguchi Y, Sakakibara M, Kano M, Taga S, Soen M, Ozaki H, Asano T, Sasaki H, Miyata T, Yasuda Y, Kobayashi T, Sugiyama M, Onoue T, Takagi H, Hagiwara D, Iwama S, Arima H,
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Journal Title
Stem Cell Reports
Volume: 18
Issue: 4
Pages: 869-883
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A new primate model of hypophyseal dysfunction.2021
Author(s)
Kawabata T, Suga H, Takeuchi K, Nagata Y, Sakakibara M, Ushida K, Ozone C, Enomoto A, Kawamoto I, Itagaki I, Tsuchiya H, Arima H, Wakabayashi T.
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Journal Title
Scientific Reports
Volume: 24
Issue: 1
Pages: 10729-10729
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ndoplasmic reticulum chaperone BiP/GRP78 knockdown leads to autophagy and cell death of arginine vasopressin neurons in mice2020
Author(s)
Yohei Kawaguchi, Daisuke Hagiwara, Takashi Miyata, Yuichi Hodai, Junki Kurimoto, Hiroshi Takagi, Hidetaka Suga, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Yoshihiro Ito, Shintaro Iwama, Ryoichi Banno, Valery Grinevich, Hiroshi Arima
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 19730-19730
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Making a Pituitary Gland in a Dish2020
Author(s)
Hidetaka Suga, Hiroshi Arima.
Organizer
The 17th Asia-Oceania Congress of Endocrinology and the 8th Seoul International Congress of Endocrinology and Metabolism (AOCE-SICEM 2020)
Related Report
Int'l Joint Research / Invited
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