Generation of hypothalamic neural stem cells in vitro from human pluripotent stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08859
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Nagoya University
• Principal Investigator: Suga Hidetaka 名古屋大学, 医学系研究科, 准教授 (20569818)
• Co-Investigator(Kenkyū-buntansha): 有馬 寛 名古屋大学, 医学系研究科, 教授 (50422770)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ヒト多能性幹細胞 / 視床下部 / 幹細胞 / 神経幹細胞

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.

Free Research Field

内分泌学、再生医学、発生学

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。