Efficient Induction of Functional Ameloblasts from Human Keratinocyte Stem Cells

Hu, Xuefeng; Lee, Jyh-Wei; Zheng, Xi-Long; Zhang, Junhua; Xiao-qin, Lin; Song, Yingnan; Wang, Bingmei; Hu, Xiaoxiao; Chang, Hao Hueng; Chena, YiPing; Lin, Chang‐Ching; Zhang, Yanding

doi:10.4172/2157-7633.1000406

Cited by 3 publications

(4 citation statements)

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“…Our previous studies have showed that epithelial sheets of human keratinocyte stem cells, when recombined with E13.5 mouse dental mesenchyme, can be induced to differentiate into enamel-secreting ameloblasts in only 10 days and apoptotically degraded in 4 weeks to achieve small-sized chimeric teeth with similar size to mouse ones, whereas the mouse secondary branchial arch epithelium, when recombined with the human dental mesenchyme from the bell-stage, remains in an enamel-secreting status after 15-week ex vivo culture and acquired large-sized teeth in the end, a size similar to human deciduous teeth (30,38,39) . These results strongly imply that the duration of epithelial differentiation and size control in tooth development could be dominated by the mesenchymal component in humans and mice.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, our recent studies showed that, in comparison with natural developmental pace, the differentiation duration of the mouse dental epithelium or non-dental epithelium into ameloblasts when induced by the human dental mesenchyme is significantly extended, whereas that of the human dental epithelium or epithelial stem cells into 22 / 45 ameloblasts when induced by the mouse dental mesenchyme is significantly shortened (38,39) . These results are consistent with the difference of development progression speed between human and mouse teeth (11) , suggesting a dominant role of the dental mesenchyme in regulation of tooth developmental tempo.…”

Section: Discussionmentioning

confidence: 99%

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FGF8-mediated signaling regulates tooth developmental pace during odontogenesis

Lin

Ruan

et al. 2020

Preprint

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The current understanding of the regulatory mechanism of organ growth is almost based on Drosophila melanogaster. In the present study, we manipulated heterotypic recombination between human and mouse dental tissues and found that the dental mesenchyme is the principal component to dominate the tooth development rate and size and FGF8 could be a critical player in this process. Forced activation of dental mesenchymal Fgf8 signaling in mice promotes the transition of the cell cycle from G1 to S-phase via p38 and perhaps PI3K-Akt intracellular signaling, resulting in promotion of cell proliferation and prevention of cell apoptosis, and thus slowdown the tooth growth rate and enlarge the tooth size. Our results provide evidences, for the first time to our knowledge, that dental mesenchymal FGF8 may be a critical intrinsic factor in controlling tooth growth rate and size during mammalian odontogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

FGF8-mediated signaling regulates tooth developmental pace during odontogenesis

Lin

Ruan

et al. 2020

Preprint

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“…Similarly, enamel regeneration might also be feasible by using foreskin derived epidermal stem cells. In fact, cultured epidermal stem cells derived from skin have been shown to differentiate into functional ameloblasts in vitro 52 . Overall, these findings, elucidate novel possibilities to develop strategies to overcome hair and enamel associated diseases.…”

Section: Discussionmentioning

confidence: 99%

Mediator 1 ablation induces enamel-to-hair lineage conversion through enhancer dynamics

Thaler

Yoshizaki

Nguyen

et al. 2022

Preprint

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Adult stem cell fate has been postulated to be primarily determined by the local tissue microenvironment. Here, we found that Mediator 1 (Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelial stem cells. Conditional loss of Med1, a key component of the Mediator complex linking enhancer activities to gene transcription, provokes a tissue extrinsic lineage shift, causing hair generation in the dental environment. Mechanistically, we found that Med1 establishes super-enhancers that control enamel lineage driven transcription factors in control dental stem cells and progenies. However, Med1 deficiency ablates this epigenetic circuit and causes a switch from the dental epithelial transcriptional program towards hair and epidermis on incisors in vivo, and in dental stem cell culture in vitro. Med1 loss also provokes an increase in enhancers and super-enhancers near epidermal and hair genes. Interestingly, control incisors already exhibit enhancers near hair and epidermal key transcription factors; these expand in size and transform into super-enhancers upon Med1 loss indicating that these epigenetic mechanisms cause the transcriptomic and phenotypic shift towards epidermal and hair lineages. Thus, we propose a role for Med1 as safeguard of the tissue-specific epigenome during adult stem cell differentiation, highlight the central role of enhancer accessibility and usage in adult stem cell lineage and provide new insights into ectodermal regeneration.

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“…The formed dental epithelium, when mixed with mouse embryonic dental mesenchyme and transplanted into renal capsules for thirty days, subsequently generated teeth-like structures, including dentin and enamel, with an incisor-like appearance [28]. Similarly, human keratinocyte stem cells when combined with embryonic mouse dental mesenchyme, sonic hedgehog (SHH), and fibroblast growth factor 8-(Fgf8-) soaked agarose beads as reconstructed tooth germs [62] and transplanted into mice renal capsules, demonstrated ameloblastic differentiation with enamel deposition. Mouse induced pluripotent stem cells demonstrated a differentiation into ameloblast-like cells, using epithelial rests of Malassez cell-conditioned medium and gelatin-coated dishes, with high expression of amelogenin, ameloblastin, and keratin 14 [63].…”

Section: Enamel Regenerationmentioning

confidence: 99%

Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update

Ahmed

Abouauf

AbuBakr

et al. 2020

Stem Cells International

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Stem/progenitor cells are undifferentiated cells characterized by their exclusive ability for self-renewal and multilineage differentiation potential. In recent years, researchers and investigations explored the prospect of employing stem/progenitor cell therapy in regenerative medicine, especially stem/progenitor cells originating from the oral tissues. In this context, the regeneration of the lost dental tissues including enamel, dentin, and the dental pulp are pivotal targets for stem/progenitor cell therapy. The present review elaborates on the different sources of stem/progenitor cells and their potential clinical applications to regenerate enamel, dentin, and the dental pulpal tissues.

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Efficient Induction of Functional Ameloblasts from Human Keratinocyte Stem Cells

Cited by 3 publications

References 0 publications

FGF8-mediated signaling regulates tooth developmental pace during odontogenesis

FGF8-mediated signaling regulates tooth developmental pace during odontogenesis

Mediator 1 ablation induces enamel-to-hair lineage conversion through enhancer dynamics

Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update

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