Self-formation of functional adenohypophysis in three-dimensional culture

Hidetaka Suga, Taisuke Kadoshima, Maki Minaguchi, Masatoshi Ohgushi, Mika Soen, Tokushige Nakano, Nozomu Takata, Takafumi Wataya, Keiko Muguruma, Hiroyuki Miyoshi, Shigenobu Yonemura, Yutaka Oiso and Yoshiki Sasai ()
Additional contact information
Hidetaka Suga: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Taisuke Kadoshima: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Maki Minaguchi: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Masatoshi Ohgushi: RIKEN Center for Developmental Biology
Mika Soen: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Tokushige Nakano: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Nozomu Takata: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Takafumi Wataya: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Keiko Muguruma: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology
Hiroyuki Miyoshi: Subteam for Manipulation of Cell Fate, BioResource Center, RIKEN
Shigenobu Yonemura: Electron Microscopy Laboratory, RIKEN Center for Developmental Biology
Yutaka Oiso: Graduate School of Medicine, Nagoya University
Yoshiki Sasai: Neurogenesis and Organogenesis Group, RIKEN Center for Developmental Biology

Nature, 2011, vol. 480, issue 7375, 57-62

Abstract: Abstract The adenohypophysis (anterior pituitary) is a major centre for systemic hormones. At present, no efficient stem-cell culture for its generation is available, partly because of insufficient knowledge about how the pituitary primordium (Rathke’s pouch) is induced in the embryonic head ectoderm. Here we report efficient self-formation of three-dimensional adenohypophysis tissues in an aggregate culture of mouse embryonic stem (ES) cells. ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, and treated with hedgehog signalling. Self-organization of Rathke’s-pouch-like three-dimensional structures occurred at the interface of these two epithelia, as seen in vivo, and various endocrine cells including corticotrophs and somatotrophs were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotrophin releasing hormone and, when grafted in vivo, these cells rescued the systemic glucocorticoid level in hypopituitary mice. Thus, functional anterior pituitary tissue self-forms in ES cell culture, recapitulating local tissue interactions.

Date: 2011
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DOI: 10.1038/nature10637

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