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2.3 Construction of Human Cerebellar Disease Models
with Patient-Derived iPSCs
Construction of neuronal disease models with hPSCs has been extensively studied
by many researchers. It depends primarily on the presence of efficient differentia-
tion protocols (Aurbry et al. 2008 ; Chambers et al. 2012 ; Corti et al. 2012 ; Delli
Carri et al. 2013 ; Devlin et al. 2015 ; Egawa et al. 2012 ; Hu and Zhang 2009 ; Israel
et al. 2012 ; Jeon et al. 2012 ; Kriks et al. 2011 ; Kondo et al. 2013 ; Kondo et al. 2014 ;
Fig. 2.5 Self-organization of the cerebellar plate neuroepithelium from hESCs. (a) qPCR analysis
for region-specific genes in hESC aggregate cultured for 21 days with or without Fgf2. Each bar
represents mean ± SD. (b and c) Immunostaining for Otx2, Gbx2, and N-cadherin of hESC aggre-
gates (day 21) cultured with or without Fgf2. (d) Expression of Kirrel2 and N-cadherin in the
aggregate on day 35. (e) Expression of cerebellar progenitor-specific markers in Fgf2-treated
aggregate on day 35. (f) Immunostaining of the aggregates on day 35. Atoh1 was expressed within
and in the periphery of Kirrel2+ cerebellar plate neuroepithelium. (g) Immunostaining of dissociated
coculture of hESC-derived progenitors with mouse granule cells. L7+ neurons appeared on day 15.
(h, i) Immunostaining of hESC-derived Purkinje cells on culture day 113. The scale bars represent
100 μm (b–d, g, h), 50 μm (f), 25 μm (e), and 5 μm (i) (Modified from Muguruma et al. 2015 )
K. Muguruma