Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells

Ozone, Chikafumi; Suga, Hidetaka; Eiraku, Mototsugu; Kadoshima, Taisuke; Yonemura, Shigenobu; Takata, Nozomu; Oiso, Yutaka; Tsuji, Takashi; Sasai, Yoshiki

doi:10.1038/ncomms10351

Cited by 169 publications

(149 citation statements)

References 37 publications

(55 reference statements)

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“…Together, SHH signaling is essential for pituitary specification by driving the earliest stages of pituitary development and regulating the early progenitor cells. In agreement, development of pituitary-phenotypical cells from pluripotent stem cells invariably requires activation of the SHH pathway (Suga et al 2011, Dincer et al 2013, Ozone et al 2016, Zimmer et al 2016.…”

Section: Sonic Hedgehog: Regulator Of Adult Pituitary Stem Cell Prolimentioning

confidence: 82%

Pituitary stem cell regulation: who is pulling the strings?

Cox

Roose

Vennekens

et al. 2017

Journal of Endocrinology

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The pituitary gland plays a pivotal role in the endocrine system, steering fundamental processes of growth, metabolism, reproduction and coping with stress. The adult pituitary contains resident stem cells, which are highly quiescent in homeostatic conditions. However, the cells show marked signs of activation during processes of increased cell remodeling in the gland, including maturation at neonatal age, adaptation to physiological demands, regeneration upon injury and growth of local tumors. Although functions of pituitary stem cells are slowly but gradually uncovered, their regulation largely remains virgin territory. Since postnatal stem cells in general reiterate embryonic developmental pathways, attention is first being given to regulatory networks involved in pituitary embryogenesis. Here, we give an overview of the current knowledge on the NOTCH, WNT, epithelial-mesenchymal transition, SHH and Hippo pathways in the pituitary stem/progenitor cell compartment during various (activation) conditions from embryonic over neonatal to adult age. Most information comes from expression analyses of molecular components belonging to these networks, whereas functional extrapolation is still very limited. From this overview, it emerges that the 'big five' embryonic pathways are indeed reiterated in the stem cells of the 'lazy' homeostatic postnatal pituitary, further magnified en route to activation in more energetic, physiological and pathological remodeling conditions. Increasing the knowledge on the molecular players that pull the regulatory strings of the pituitary stem cells will not only provide further fundamental insight in postnatal pituitary homeostasis and activation, but also clues toward the development of regenerative ideas for improving treatment of pituitary deficiency and tumors.

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Section: Sonic Hedgehog: Regulator Of Adult Pituitary Stem Cell Prolimentioning

confidence: 82%

Pituitary stem cell regulation: who is pulling the strings?

Cox

Roose

Vennekens

et al. 2017

Journal of Endocrinology

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“…There are currently several published studies in which hPSCs are differentiated into organoids of various tissues including stomach [119], intestine [120–122], liver [46, 123, 124], lung [125], brain [126], anterior pituitary [127], and kidneys [3, 6, 7, 19, 51]. Here, we summarize four studies that generated kidney organoids from hPSCs (Key Figure, Figure 3, and Figure 4).…”

Section: Comparison Of Kidney Organoid Differentiation Protocolsmentioning

confidence: 99%

Kidney Organoids: A Translational Journey

Morizane

Bonventre

2017

Trends in Molecular Medicine

120

110

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Human pluripotent stem cells (hPSCs) are attractive sources for regenerative medicine and disease modeling in vitro. Directed hPSC differentiation approaches have derived from knowledge of cell development in vivo rather than from stochastic cell differentiation. Moreover, there has been great success in the generation of 3-dimensional organ-buds termed “organoids” from hPSCs; these consist of a variety of cell types in vitro to mimic organs in vivo. The organoid bears great potential in the study of human diseases in vitro especially when combined with CRISPR/Cas9-based genome editing approaches. We summarize the current literature describing organoid studies with a special focus on kidney organoids, and discuss goals and future opportunities for organoid-based studies.

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“…Recent studies demonstrated a derivation of anterior pituitary hormone-producing cells from human embryonic or induced pluripotent stem cells, which are able to function in response to stimulus in murine hypopituitarism models [8, 12], with the two-dimensional approach by Zimmer et al [12] generating functional cells at higher efficiency. In order for in vitro-generated cells to achieve homeostatic control in vivo, these have to be grafted within the pituitary or in immediate contact with the hypothalamus [13-16].…”

Section: Generation Of Pituitary Endocrine Cells From Pluripotent Stementioning

confidence: 99%

Basic Research Advances on Pituitary Stem Cell Function and Regulation

Russell¹,

Lodge²,

Andoniadou³

2018

Neuroendocrinology

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As a central regulator of major physiological processes, the pituitary gland is a highly dynamic organ, capable of responding to hormonal demand and hypothalamic influence, through adapting secretion as well as remodelling cell numbers among its seven populations of differentiated cells. Stem cells of the pituitary have been shown to actively generate new cells during postnatal development but remain mostly quiescent during adulthood, where they persist as a long-lived population. Despite a significant body of research characterising attributes of anterior pituitary stem cells, the regulation of this population is poorly understood. A better grasp on the signalling mechanisms influencing stem proliferation and cell fate decisions can impact on our future treatments of pituitary gland disorders such as organ failure and pituitary tumours, which can disrupt endocrine homeostasis with life-long consequences. This minireview addresses the current methodologies aiming to understand better the attributes of pituitary stem cells and the normal regulation of this population in the organ, and discusses putative future avenues to manipulate pituitary stem cells during disease states or regenerative medicine approaches.

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Functional anterior pituitary generated in self-organizing culture of human embryonic stem cells

Cited by 169 publications

References 37 publications

Pituitary stem cell regulation: who is pulling the strings?

Pituitary stem cell regulation: who is pulling the strings?

Kidney Organoids: A Translational Journey

Basic Research Advances on Pituitary Stem Cell Function and Regulation

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