RRC ID 37111
Author Suga H, Kadoshima T, Minaguchi M, Ohgushi M, Soen M, Nakano T, Takata N, Wataya T, Muguruma K, Miyoshi H, Yonemura S, Oiso Y, Sasai Y.
Title Self-formation of functional adenohypophysis in three-dimensional culture.
Journal Nature
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.
Volume 480(7375)
Pages 57-62
Published 2011-11-9
DOI 10.1038/nature10637
PII nature10637
PMID 22080957
MeSH Animals Cell Culture Techniques Cell Line Cell Lineage Cells, Cultured Ectoderm / cytology Ectoderm / embryology Embryonic Stem Cells / cytology* Endocrine Cells / cytology Endocrine Cells / metabolism Hypopituitarism / pathology Hypothalamus / cytology Hypothalamus / embryology Mice Pituitary Gland, Anterior / cytology* Pituitary Gland, Anterior / embryology*
IF 42.779
Times Cited 274
DNA material CS-RfA-ETR (RDB08362) pENTR4-H1tetOx1 (RDB07916) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)