title: Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells.
abstract: During cerebellar development, the main portion of the cerebellar plate neuroepithelium gives birth to Purkinje cells and interneurons, whereas the rhombic lip, the germinal zone at its dorsal edge, generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components cooperate to form the intricate cerebellar structure. Here, we found that a polarized cerebellar structure self-organizes in 3D human embryonic stem cell (ESC) culture. The self-organized neuroepithelium differentiates into electrophysiologically functional Purkinje cells. The addition of fibroblast growth factor 19 (FGF19) promotes spontaneous generation of dorsoventrally polarized neural-tube-like structures at the level of the cerebellum. Furthermore, addition of SDF1 and FGF19 promotes the generation of a continuous cerebellar plate neuroepithelium with rhombic-lip-like structure at one end and a three-layer cytoarchitecture similar to the embryonic cerebellum. Thus, human-ESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellum at the first trimester.
authors: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan. Electronic address: muguruma@cdb.riken.jp.
authors: Keiko
authors: K
authors: Muguruma
authors: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors: Ayaka
authors: A
authors: Nishiyama
authors: Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, 734-8551, Japan.
authors: Hideshi
authors: H
authors: Kawakami
authors: Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, 734-8551, Japan.
authors: Kouichi
authors: K
authors: Hashimoto
authors: Laboratory for Organogenesis and Neurogenesis, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors: Yoshiki
authors: Y
authors: Sasai
mesh_terms: D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism*; D011689:Purkinje Cells / Q000166:cytology
chemical_list: D054377:Chemokine CXCL12; C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors