Human pituitary development and application of iPSCs for pituitary disease
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Cellular and Molecular Life Sciences
REVIEW
Human pituitary development and application of iPSCs for pituitary disease Ryusaku Matsumoto1,2 · Yutaka Takahashi1,3 Received: 30 June 2020 / Revised: 23 October 2020 / Accepted: 26 October 2020 © Springer Nature Switzerland AG 2020
Abstract The pituitary plays a pivotal role in maintaining systemic homeostasis by secreting several hormones. During fetal development, the pituitary develops from the oral ectoderm in contact with the adjacent hypothalamus. This process is regulated by the fine-tuned expression of transcription and growth factors. Impairments of this process result in congenital pituitary hypoplasia leading to dysfunction of the pituitary. Although animal models such as knockout mice have helped to clarify these underlying mechanisms, the developmental processes of the human pituitary gland and the mechanisms of human pituitary disorders have not been fully understood. This is because, at least in part, of the lack of a human pituitary developmental model. Recently, methods for in vitro induction of the pituitary gland from human pluripotent stem cells were developed. These models can be utilized not only for regenerative medicine but also for human pituitary studies on developmental biology and for modeling of pituitary disorders, such as hypopituitarism and pituitary tumors. In this review, we provide an overview of recent progress in the applications of pluripotent stem cells for pituitary research and discuss further perspectives for pituitary studies. Keywords Pituitary development · Induced pluripotent stem cell · Organoid culture · Developmental biology · Disease modeling
Introduction The pituitary gland plays a pivotal role in maintaining systemic homeostasis by regulating pituitary hormones. A large number of studies have clarified the fundamental cellular and molecular mechanisms of pituitary development and the underlying mechanisms of pituitary diseases. However, these studies on pituitary development are mainly based on model animals, including mouse, rat, chicken, and zebra fish. Therefore, the mechanisms of pituitary development in humans are not yet fully understood. The developmental process of the human pituitary is considered to share many of the mechanisms found in animals; however, there are * Yutaka Takahashi takahash@naramed‑u.ac.jp 1
Department of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan
2
Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan
3
Department of Diabetes and Endocrinology, Nara Medical University, 840 Shijo‑cho, Kashihara, Nara 634‑8522, Japan
significant species-specific differences, including developmental time scale, gene expression pattern, and phenotypes resulting from gene mutations. A number of pituitary disorders have an unknown etiology. For example, only 5% of patients with congenital hypopituitarism revealed causal gene mutations even by comprehensive analysis using next-generation sequencing, and the cause of the remaini
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