© Springer Nature Singapore Pte Ltd. 2017 41
T. Tsuji (ed.), Organ Regeneration Based on Developmental Biology,
DOI 10.1007/978-981-10-3768-9_3
Chapter 3
Functional Pituitary Tissue Formation
Recapitulating Hypothalamus and Pituitary
Development Using ES/iPS Cells
Hidetaka Suga and Chikafumi Ozone
Abstract The hypothalamic-pituitary system is essential for maintaining homeo-
stasis by controlling systemic hormones. However, it can be disrupted by various
diseases, resulting in lifelong serious symptoms.
Pluripotent stem cells, such as embryonic stem (ES) cells and induced pluripo-
tent stem (iPS) cells, differentiate into neuroectodermal progenitors when cultured
as floating aggregates under serum-free conditions. Recent results have shown that
strict removal of exogenous patterning factors induces efficient generation of rostral
hypothalamic progenitors from mouse ES cells. Those hypothalamic-like progeni-
tors generated rostral-dorsal hypothalamic neurons, in particular magnocellular
vasopressinergic neurons, which release hormones upon stimulation.
We subsequently reported self-formation of adenohypophysis using mouse ES
cell aggregates. The aggregates were stimulated to differentiate into both non-neural
head ectoderm and hypothalamic neuroectoderm in adjacent layers, followed by
treatment with a Sonic Hedgehog agonist. Self-organization of Rathke’s pouch-like
structures occurred at the interface of the two epithelia in vitro. Subsequently, vari-
ous endocrine cells including corticotrophs were produced from Rathke’s pouch-
like structures. The induced corticotrophs efficiently secreted adrenocorticotropic
hormone in response to corticotropin-releasing hormone. Furthermore, when
engrafted in vivo, these cells rescued systemic glucocorticoid levels in hypopitu-
itary mice.
H. Suga (*)
Department of Endocrinology and Diabetes, Graduate School of Medicine,
Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aich 466-8550, Japan
e-mail: [email protected]
C. Ozone
Department of Endocrinology and Diabetes, Graduate School of Medicine,
Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya, Aich 466-8550, Japan
RIKEN Center for Developmental Biology, Kobe 650-0047, Hyogo, Japan