BMP4 and FGF strongly induce differentiation of mouse ES cells into oral ectoderm

Ochiai, Hiroshi; Suga, Hidetaka; Yamada, Takanobu; Sakakibara, Makoto; Kasai, Takatoshi; Ozone, Chikafumi; Ogawa, Kazuko; Goto, Motomitsu; Banno, Ryoichi; Tsunekawa, Shin; Sugimura, Yoshihisa; Arima, Hiroshi; Oiso, Yutaka

doi:10.1016/j.scr.2015.06.011

Cited by 24 publications

(18 citation statements)

References 35 publications

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“…1a; Koehler et al 2013), which belongs to the head and oral ectoderm, following BMP treatment of mouse ES cells, which supports the reliability and robustness of this strategy. Our recent study showed that very low concentrations (picomolar level) of exogenous BMP4 treatment facilitated differentiation into non-neural ectoderms, which contained not only pituitary primordium but also dental germs (Ochiai et al 2015). Taken together, these findings appear to indicate that appropriate BMP4 expression is important for head ectoderm induction (Wilson and Hemmati-Brivanlou 1995;Basch and Bronner-Fraser 2006;Davis and Camper 2007).…”

Section: Two-layer Formation In Vitro Is the First Step Of Adenohypohmentioning

confidence: 79%

Recapitulating Hypothalamus and Pituitary Development Using Embryonic Stem/Induced Pluripotent Stem Cells

Suga

2016

Stem Cells in Neuroendocrinology

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The hypothalamic-pituitary system is essential for maintaining life and controlling systemic homeostasis. However, it can be negatively affected by various diseases, resulting in life-long serious symptoms.Pluripotent stem cells, such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, differentiate into neuroectodermal progenitors when cultured as floating aggregates under serum-free conditions.Recent results have shown that strict removal of exogenous patterning factors during the early differentiation period induces efficient generation of rostral hypothalamic-like progenitors from mouse ES cell-derived neuroectodermal cells. The use of growth factor-free, chemically defined medium was critical for this induction. The ES cell-derived hypothalamic-like progenitors generated rostraldorsal hypothalamic neurons, in particular magnocellular vasopressinergic neurons, which release hormones upon stimulation.We subsequently reported efficient self-formation of three-dimensional adenohypophysis tissues in aggregate cultures of mouse ES cells. The ES cells were stimulated to differentiate into non-neural head ectoderm and hypothalamic neuroectoderm in adjacent layers within the aggregate, followed by treatment with a Sonic Hedgehog agonist. Self-organization of Rathke's pouch-like structures occurred at the interface of the two epithelia in vivo, and various endocrine cells, including corticotrophs and somatotrophs, were subsequently produced. The corticotrophs efficiently secreted adrenocorticotropic hormone in response to corticotropin-releasing hormone. Furthermore, when engrafted in vivo, these cells rescued systemic glucocorticoid levels in hypopituitary mice.The present study aimed to prepare hypothalamic and pituitary tissues from human pluripotent stem cells and establish effective transplantation techniques for future clinical applications. Preliminary results indicated differentiation using human ES/iPS cells, and the culture method replicated stepwise embryonic differentiation. Therefore, these methods could potentially be used as developmental and disease models as well as for future regenerative medicine.

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Section: Two-layer Formation In Vitro Is the First Step Of Adenohypohmentioning

confidence: 79%

Recapitulating Hypothalamus and Pituitary Development Using Embryonic Stem/Induced Pluripotent Stem Cells

Suga

2016

Stem Cells in Neuroendocrinology

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“…Transplantation of differentiated aggregates under the kidney capsule in hypophysectomised mice improved cortisol deficiency symptoms, which demonstrated the functionality of the ESC-derived corticotrophs (Suga et al 2011). Obtaining other endocrine cell types was initially less efficient (Suga et al 2011); however, addition of BMP and FGF improves both corticotroph and Pit-1 lineage endocrine cell differentiation (Ochiai et al 2015).…”

Section: Induction Of Rp From 3d Aggregatesmentioning

confidence: 96%

“…Following their success with generation of hypothalamic-like tissue (Wataya et al 2008), Suga et al (2011) reasoned that, by further inducing rostral character, they should obtain a domain equivalent to the anterior neural ridge apposed to a neurectoderm-like tissue, where RP formation may be induced (Ochiai et al 2015;see Suga 2016). Large ESC aggregates were made in growth factor-free medium in the presence of SHH agonist, resulting in formation of a superficial ectodermal layer surrounding a RAX-positive neurectodermal domain.…”

Section: Induction Of Rp From 3d Aggregatesmentioning

confidence: 99%

“…Large ESC aggregates were made in growth factor-free medium in the presence of SHH agonist, resulting in formation of a superficial ectodermal layer surrounding a RAX-positive neurectodermal domain. Subsequently, ectodermal patches thickened, RP marker expression was induced, and invagination of RP-like structures was observed, more efficiently in the presence of both BMP and FGF (Ochiai et al 2015). The positive action of these two factors fits with in vivo requirements, because these are secreted from the infundibulum and necessary for RP induction and maintenance, respectively (Ericson et al 1998;Treier et al 1998).…”

Section: Induction Of Rp From 3d Aggregatesmentioning

confidence: 99%

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Perspective on Stem Cells in Developmental Biology, with Special Reference to Neuroendocrine Systems

Rizzoti

Pires

Lovell‐Badge

2016

Stem Cells in Neuroendocrinology

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In the embryo, organs gradually take shape as tissue progenitors, proliferate, differentiate and are organised, via cellular interactions, in tri-dimensional functional structures. Most adult organs retain a cell population sharing important similarities with embryonic progenitors, which includes the ability to both selfrenew and to differentiate into the full range of the specialised cell types corresponding to the organ in which they reside. These two essential properties define them as adult stem cells (AdSC). Their characterization in different contexts provides a better understanding of cell turnover modalities for organ function, which is important for tumorigenesis, because adult tissue stem cells can give rise to cancer stem cells. However, it is also relevant to regenerative medicine, because stem cells can be transplanted or manipulated in vivo to restore missing cells. The successful reprogramming of somatic cells into induced pluripotent stem cells (iPSC) (Takahashi and Yamanaka, Cell 126:663-676, 2006), resembling pluripotent embryonic stem cells (ESC), opened alternative strategies for cell replacement. The required cell type can be differentiated in vitro from expandable progenitors and transplanted where required. This approach is particularly promising, because genetic defects can potentially be repaired in vitro prior to their engraftment; moreover, a large number of cells can be produced (Fox et al., Science 345:1247391, 2014). However, the transplanted cells have to be able to functionally integrate into the deficient organ. To potentially alleviate this problem, tri-dimensional culture systems have been recently developed where mini-organs, or organoids, can be obtained in vitro. These also represent unique models for disease modelling and drug screening (Huch and Koo, Development 142:3113-3125, 2015). Within neuroendocrine systems, the hypothalamo-pituitary axis has a crucial role for body homeostasis. It also regulates functions such as growth, reproduction, stress and, more generally, metabolism. The hypothalamus centralizes information from the periphery and other brain regions to regulate pituitary hormone secretions and to control appetite, sleep and aging. Its functions are exerted through secretion of neurohormones and manipulation of these could be of interest not only for the treatment of obesity and sleep disorders but also to alleviate aging-related conditions. Pituitary hormone deficiencies can originate from defects affecting the hypothalamus, pituitary, or both. Today these deficiencies are treated by substitution or replacement therapies, which are costly and have side effects. AdSC have recently been characterized in the hypothalamus and pituitary (Castinetti et al., Endocr Rev 32:453-471, 2011; Bolborea and Dale, Trends Neurosci 36:91-100, 2013). Moreover, hypothalamic neurons and pituitary endocrine cells have been differentiated in vitro from ESC and iPSC and successfully transplanted. These promising routes for development of regenerative medicine to restore ...

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“…Fang et al and Liu et al [21, 22] successfully generated ameloblast-like cells from mouse iPS cells using ameloblast serum-free conditioned medium (ASF-CM) supplemented with BMP4 to promote odontogenic differentiation. Ochiai et al [23] found that treatment with BMP4 and FGF8 improved oral ectoderm differentiation from mES cells and that a high BMP4 concentration induces dental epithelium and mesenchyme differentiation. Using custom culture media, Cai et al [24] differentiated human iPS cells and H1-ES cells into an epithelial sheet that exhibited odontogenic potential when combined with E14.5 mouse dental mesenchyme, although the probability of tooth formation was low.…”

Section: Introductionmentioning

confidence: 99%

Generation of tooth–periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells

Zhang

Shi

et al. 2017

Stem Cell Res Ther

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BackgroundA number of studies have shown that tooth-like structures can be regenerated using induced pluripotent stem cells and mouse embryonic stem (mES) cells. However, few studies have reported the regeneration of tooth–periodontium complex structures, which are more suitable for clinical tooth transplantation. We established an optimized approach to induce high-odontogenic potential dental epithelium derived from mES cells by temporally controlling bone morphogenic protein 4 (BMP4) function and regenerated tooth–periodontium complex structures in vivo.MethodsFirst, immunofluorescence and quantitative reverse transcription-polymerase chain reaction were used to identify the watershed of skin and the oral ectoderm. LDN193189 was then used to inhibit the BMP4 receptor around the watershed, followed by the addition of exogenous BMP4 to promote BMP4 function. The generated dental epithelium was confirmed by western blot analysis and immunofluorescence. The generated epithelium was ultimately combined with embryonic day 14.5 mouse mesenchyme and transplanted into the renal capsules of nude mice. After 4 weeks, the tooth–periodontium complex structure was examined by micro-computed tomography (CT) and hematoxylin and eosin (H&E) staining.ResultsOur study found that the turning point of oral ectoderm differentiation occurred around day 3 after the embryoid body was transferred to a common culture plate. Ameloblastin-positive dental epithelial cells were detected following the temporal regulation of BMP4. Tooth–periodontium complex structures, which included teeth, a periodontal membrane, and alveolar bone, were formed when this epithelium was combined with mouse dental mesenchyme and transplanted into the renal capsules of nude mice. Micro-CT and H&E staining revealed that the generated tooth–periodontium complex structures shared a similar histological structure with normal mouse teeth.ConclusionsAn optimized induction method was established to promote the differentiation of mES cells into dental epithelium by temporally controlling the function of BMP4. A novel tooth–periodontium complex structure was generated using the epithelium.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0583-5) contains supplementary material, which is available to authorized users.

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BMP4 and FGF strongly induce differentiation of mouse ES cells into oral ectoderm

Cited by 24 publications

References 35 publications

Recapitulating Hypothalamus and Pituitary Development Using Embryonic Stem/Induced Pluripotent Stem Cells

Recapitulating Hypothalamus and Pituitary Development Using Embryonic Stem/Induced Pluripotent Stem Cells

Perspective on Stem Cells in Developmental Biology, with Special Reference to Neuroendocrine Systems

Generation of tooth–periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells

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