Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors

Ogawa, Kazuko; Suga, Hidetaka; Ozone, Chikafumi; Sakakibara, Makoto; Yamada, Takanobu; Kano, Mayuko; Mitsumoto, Kazuki; Kasai, Takatoshi; Kodani, Yu; Nagasaki, Hiroshi; Yamamoto, Naoki; Hagiwara, Daisuke; Goto, Motomitsu; Banno, Ryoichi; Sugimura, Yoshihisa; Arima, Hiroshi

doi:10.1038/s41598-018-22053-x

Cited by 29 publications

(33 citation statements)

References 34 publications

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“…These data indicated that the hybrid aggregates were comparable with the in vivo pituitary gland, at least with regard to their ACTH secretion capacity. Furthermore, we modified the culture medium for hypothalamic differentiation ( Figure 3J) on the basis of our previous study (Ogawa et al, 2018). As a result, increased CRH induction ( Figure 3K) appeared to promote ACTH maturation ( Figure 3L).…”

Section: Simultaneous Development Of Both Anterior Pituitary and Hypomentioning

confidence: 99%

Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells

et al. 2020

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Highlights d Hypothalamic-pituitary functional units can be generated from 3D-cultured human iPS cells d Maturation of induced pituitary through simultaneous culture with hypothalamic neurons d ACTH secretion ability of induced pituitary is comparable with adult mice d Induced pituitary cells respond to low-glucose stimulation through the CRH-ACTH pathway SUMMARYThe pituitary is a major hormone center that secretes systemic hormones responding to hypothalamusderived-releasing hormones. Previously, we reported the independent pituitary induction and hypothalamic differentiation of human embryonic stem cells (ESCs).Here, a functional hypothalamic-pituitary unit is generated using human induced pluripotent stem (iPS) cells in vitro. The adrenocorticotropic hormone (ACTH) secretion capacity of the induced pituitary reached a comparable level to that of adult mouse pituitary because of the simultaneous maturation with hypothalamic neurons within the same aggregates. Corticotropin-releasing hormone (CRH) from the hypothalamic area regulates ACTH cells similarly to our hypothalamic-pituitary axis. Our induced hypothalamic-pituitary units respond to environmental hypoglycemic condition in vitro, which mimics a lifethreatening situation in vivo, through the CRH-ACTH pathway, and succeed in increasing ACTH secretion. Thus, we generated powerful hybrid organoids by recapitulating hypothalamic-pituitary development, showing autonomous maturation on the basis of interactions between developing tissues.

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Section: Simultaneous Development Of Both Anterior Pituitary and Hypomentioning

confidence: 99%

Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells

et al. 2020

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“…Because of the short fetal development duration, mouse ES cells have a short developmental period. Mouse ES cells differentiate into hypothalamus and pituitary in ~30 days (Suga et al., 2011; Wataya et al., 2008), whereas human ES cells differentiate into these tissues in ~90 days to150 days (Ogawa et al., 2018; Ozone et al., 2016). Mouse ES cells are therefore suitable for establishing novel differentiation methods with numerous trial‐and‐error processes.…”

Section: Three‐dimensional Differentiation Culture Methods From Es Celmentioning

confidence: 99%

Hypothalamic–pituitary organoid generation through the recapitulation of organogenesis

2021

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The hypothalamic-pituitary system is essential for maintaining physiological homeostasis by controlling systemic hormones, but its regeneration remains mostly unclear. Therefore, attention is focused on the regeneration of the hypothalamus and pituitary from stem cells. Somatic stem cells have drawn attention for their potential for use in regenerative medicine. In the adenohypophysis, the existence of somatic stem cells was reported (Chen et al., 2005), and their functions were discussed at three phases: during early postnatal pituitary maturation (

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“…Clearly, the study of Rax in the human hypothalamus is an important goal, and may be aided through techniques for the directed differentiation of pluripotent cells (Sasai et al, 2012). Human and mouse pluripotent stem cells can be induced to differentiate into RAX/Rax-expressing hypothalamic progenitors (Wataya et al, 2008;Merkle et al, 2025;Wang et al, 2015;Ogawa et al, 2018), that can induce adenohypophysial tissue in culture (Ozone et al, 2016). This indicates that hypothalamic organoids might eventually be used to study the function of RAX during the development of the hypothalamus and the pituitary in humans.…”

Section: Rax In Human Hypothalamic and Pituitary Developmentmentioning

confidence: 99%

Conserved roles of Rax/rx3 genes in hypothalamus and pituitary development

Souza¹,

Placzek²

2021

Int. J. Dev. Biol.

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Rax (Rx) genes encode paired-type homeodomain-containing transcription factors pre-sent in virtually all metazoan groups. In vertebrates, studies in fish, amphibian, chick and mouse models have revealed that these genes play important roles in the development of structures lo-cated at the anterior portion of the central nervous system, in particular the eyes, the hypothala-mus and the pituitary gland. In addition, human patients with eye and brain defects carry muta-tions in the two human Rax paralogues, RAX and RAX2. Here, we review work done in the last years on Rax genes, focusing especially on the function that mouse Rax and its zebrafish homo-logue, rx3, play in hypothalamic and pituitary development. Work on both of these model organ-isms indicate that Rax genes are necessary for the patterning, growth and differentiation of the hypothalamus, in particular the dorso-anterior hypothalamus, where they effect their action by controlling expression of the secreted signalling protein, Sonic hedgehog (Shh). In addition, Rax/rx3 mutations disturb the development of the pituitary gland, mimicking phenotypes ob-served in human subjects carrying mutations in the RAX gene. Thus, along with their crucial role in eye morphogenesis, Rax genes play a conserved role in the development of the hypothalamus and adjacent structures in the vertebrate clade.

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Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors

Cited by 29 publications

References 34 publications

Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells

Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells

Hypothalamic–pituitary organoid generation through the recapitulation of organogenesis

Conserved roles of Rax/rx3 genes in hypothalamus and pituitary development

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