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Differentiation induction from human pluripotent stem cells to hypothalamic neurons

机译:人多能干细胞向下丘脑神经元的分化诱导

摘要

Provided is a method for efficiently inducing differentiation from human pluripotent stem cells into hypothalamic neurons. Also provided is a method for constructing a cell structure in which hypothalamic tissue and pituitary tissue are integrated from human pluripotent stem cells. Suspension culture of aggregates of human pluripotent stem cells in a medium containing a low concentration of an osteogenic factor signaling pathway activator and a low concentration of an Shh signaling pathway activator, and cell aggregation obtained in this step A cell structure containing hypothalamic tissue is obtained by a method comprising the step of further suspension culture of the mass in a medium containing a low-concentration Shh signal pathway agent. In addition, a suspension culture of aggregates of human pluripotent stem cells in a medium containing a bone morphogenetic factor signal transduction pathway activator and a Shh signal pathway agonist, and the cell aggregates formed in this step Further suspension culture in a medium containing a substance that activates the formation factor signal transduction pathway and an agent that acts on the Shh signal pathway, and the cell aggregate obtained in this step in a medium suitable for simultaneous induction of the pituitary and hypothalamus A cell structure including a hypothalamic tissue and a pituitary tissue is obtained by a method including the step of suspension culture in (1).
机译:提供了一种有效诱导人多能干细胞向下丘脑神经元分化的方法。还提供了一种构建细胞结构的方法,其中下丘脑组织和垂体组织由人多能干细胞整合而成。将人多能干细胞的聚集体悬浮在含有低浓度成骨因子信号传导途径活化剂和低浓度Shh信号传导途径活化剂的培养基中,然后在该步骤中获得细胞聚集体,通过以下方法获得含有下丘脑组织的细胞结构一种方法,包括将物质在含有低浓度Shh信号途径剂的培养基中进一步悬浮培养的步骤。另外,将人多能干细胞聚集体在含有骨形态发生因子信号转导途径激活剂和Shh信号途径激动剂的培养基中悬浮培养,并在该步骤中形成细胞聚集体。激活形成因子信号转导途径和作用于Shh信号途径的物质,并在适合同时诱导垂体和下丘脑的培养基中激活该步骤中获得的细胞聚集体,包括下丘脑组织和垂体组织的细胞结构为通过包括(1)中的悬浮培养步骤的方法获得。

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