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

By K. Muguruma, Ayaka Nishiyama, H. Kawakami, K. Hashimoto, Y. Sasai. Cell Reports, 2015

603 citations recorded by the source corpus.

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.

Subfields: Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a85027c5bd17d4952e12783758ac5a21edd35539

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Citations in the corpus

Brain organoids: advances, applications and challenges (2019, methodology): “Guided methods for generating brain organoids were pioneered by the Sasai group, who developed a series of 3D differentiation protocols based on the serum-free culture of EB-like aggregates (Table 1) (Danjo et al., 2011; Eiraku et al., 2008; Kadoshima et al., 2013; Muguruma et al., 2015; Sakaguchi e”
Modeling Development and Disease with Organoids. (2016, background): “In a subsequent study, the investigators reported that the addition of Fgf19 and SDF1 to this protocol allows human ES cells to generate a polarized structure reminiscent of the first trimester cerebellum (Muguruma et al., 2015).”
Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin producing neurons (2016, background): “These limitations have prompted the development of 3D organoid models that mimic the organization and function of brain parts using hPSCs (Lancaster et al., 2013; Mariani et al., 2015; Muguruma et al., 2015; Paşca et al., 2015; Qian et al., 2016).”
Brain Region-specific Organoids using Mini-bioreactors for Modeling ZIKV Exposure (2016, positive): “A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Mariani et al., 2015; Muguruma et al., 2015; Pasca et al., 2015) have generated much excitement for using organoids to model human brain development and disorders.”