© Springer Nature Singapore Pte Ltd. 2017 25
T. Tsuji (ed.), Organ Regeneration Based on Developmental Biology,
DOI 10.1007/978-981-10-3768-9_2
Chapter 2
Self-Organized Cerebellar Tissue from Human
Pluripotent Stem Cells and Its Application
to Clinical Medicine
Keiko Muguruma
Abstract The cerebellum is a highly ordered brain structure with several well-
defined types of cells, which are indispensable for motor functions. It is known that
the damage of the cerebellum leads to impairments in motor and postural control.
The damage is often caused by cerebellar neurodegenerative diseases that arise spo-
radically or from inherited genetic defects. The investigation of the pathophysiology
and the discovery of drugs for these diseases require the generation of accurate
disease models. However, it has been difficult to generate them due to limited infor-
mation on the human cerebellar development and unavailability of living human
cerebellar neurons in experiments.
We recently reported that cerebellar neurons are generated from human pluripo-
tent stem cells (hPSCs) such as embryonic stem cells (hESCs) and induced pluripo-
tent stem cells (iPSCs). We have developed a three-dimensional (3D) culture system
of hPSCs that recapitulates the in vivo microenvironments associated with the isth-
mic organizer, the source of self-inductive signaling. In this chapter, I explain the
cerebellar neurogenesis from hPSCs, focusing on the notion of the positional infor-
mation and self-formation of polarized neuroepithelium. I also discuss how in vitro
culture systems using hPSCs facilitate the mechanistic understanding of cerebellar
development in humans and the establishment of accurate neurodegenerative dis-
ease models.
Keywords Purkinje cells • Cerebellum • Pluripotent stem cells • Spinocerebellar
ataxia • SCA • Self-organization • Neural differentiation • Cerebellar development
K. Muguruma (*)
Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology,
2-2-3 Minatojima-minamimachi, Chuo, Kobe 650-0047, Hyogo, Japan
e-mail: [email protected]