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Self-organization of polarized cerebellar plate neuroepithelium in three-dimensional culture of human pluripotent stem cells


ABSTRACT: During cerebellar development, the main portion of the cerebellar plate neuroepithelium (NE) gives birth to Purkinje cells and interneurons, while the germinal zone at its dorsal edge, called the rhombic lip (RL), generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components work together to generate the intricate structure of the cerebellar anlage. In this study, we found that a polarized cerebellar anlage structure self-organizes in three-dimensional (3D) human ES cell (hESC) culture. This NE is capable of differentiating into electrophysiologically functional Purkinje cells. The addition of FGF19 promotes spontaneous generation of dorsoventrally polarized NE structures containing cerebellar and basal plates. Furthermore, further addition of SDF1 promoted the generation of stratified cerebellar plate NE with RL-like germinal zones self-forming at the edge. Thus, hESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellar anlage at the first trimester. Examination of mRNA profile in two different treated human ES cells .

ORGANISM(S): Homo sapiens

SUBMITTER: Keiko Muguruma 

PROVIDER: E-GEOD-63015 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Muguruma Keiko K   Nishiyama Ayaka A   Kawakami Hideshi H   Hashimoto Kouichi K   Sasai Yoshiki Y  

Cell reports 20150129 4


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 neuroepit  ...[more]

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