Self-organization of cerebellar tissue in 3D culture of human pluripotent stem cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24570242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: MUGURUMA Keiko 独立行政法人理化学研究所, 多細胞システム形成研究センター, 専門職研究員 (30209978)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 小脳 / ヒト多能性幹細胞 / 神経分化 / 3次元培養 / 自己組織化

Outline of Final Research Achievements

Purkinje cells are the sole output neurons of the cerebellar cortex and their dysfunction causes severe ataxia. We found that both Purkinje cells and granule cells could be effectively generated from human pluripotent stem (ES and iPS) cells by recapitulating the self-inducitive signaling microenvironments of the isthmic organizer. The cerebellar neuroepithelium (NE), formed in response to the combination of Fgf2 and insulin, differentiated into electrophysiologically functional Purkinje cells. The addition of Fgf19 and CXCL12 promotes the generation a continuous cerebellar plate NE and a three-layer cytoarchitecture similar to the embryonic cerebellum. Thus, human pluripotent stem cells-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum.

Free Research Field

神経発生