Hypothalamic-pituitary organoid generation through the recapitulation of organogenesis

This paper overviews the development and differentiation of the hypothalamus and pituitary gland from embryonic stem (ES) and induced pluripotent stem (iPS) cells. It is important to replicate the developmental process in vivo to create specific cells/organoids from ES/iPS cells. We also introduce the latest findings and discuss future issues for clinical application. Neuroectodermal progenitors are induced from pluripotent stem cells by strictly removing exogenous patterning factors during the early differentiation period. The induced progenitors differentiate into rostral hypothalamic neurons, in particular magnocellular vasopressin⁺  neurons. In three-dimensional cultures, ES/iPS cells differentiate into hypothalamic neuroectoderm and nonneural head ectoderm adjacently. Rathke's pouch-like structures self-organize at the interface between the two layers and generate various endocrine cells, including corticotrophs and somatotrophs. Our next objective is to sophisticate our stepwise methodology to establish a novel transplantation treatment for hypopituitarism and apply it to developmental disease models.