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Stagewise keratinocyte differentiation from human embryonic stem cells by defined signal transduction modulators

ABSTRACT: Stagewise keratinocyte differentiation from human embryonic stem cells by defined signal transduction modulators

PROVIDER: PRJNA603109 | ENA |

REPOSITORIES: ENA

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Stagewise keratinocyte differentiation from human embryonic stem cells by defined signal transduction modulators

Project description:we use human embryonic stem cells to demonstrate that epidermal ectoderm and subsequent keratinocyte cell fate can be determined step by step under the regulation of defined factors. We show the global gene expression profiles clustered according to the differentiation stages . We also found the human keratinocyte specific gene expression according to the differentiation stages.

2020-01-25 | GSE144241 | GEO

Stagewise keratinocyte differentiation from human embryonic stem cells by defined signal transduction modulators.

Project description:Keratinocyte is the predominant cell type in the epidermis of skin, and it provides the protective barrier function for the body. Various signaling pathways have been implicated in keratinocyte differentiation in animal models; However, their temporal regulation and interactions are still to be explored in pluripotent stem cell models. In this report, we use human embryonic stem cells to demonstrate that epidermal ectoderm and subsequent keratinocyte cell fate can be determined step by step under the regulation of defined factors. The inhibition of TGFβ initiates ectodermal lineage differentiation, and the activation of BMP pathway drives epidermal TP63 expression. Meanwhile, the timely activation of WNT pathway suppresses extraembryonic lineage, and promotes epidermal cell fate. With further specification by NOTCH inhibition, more than 90% of cells become TP63-positive stage Ⅱ keratinocytes. Finally, stage Ⅲ keratinocytes are produced under defined hypo-calcium keratinocyte culture conditions, and are further matured in mouse xenograft model. This study not only establishes an in vitro platform to study keratinocyte cell fate determination, but also provides an efficient protocol to produce keratinocytes for disease models and clinical applications.

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Project description:We have previously demonstrated that molecular hydrogen (H2) neutralizes hydroxyl radical (•OH) in cultured-cells and protects cells and tissues against oxidative stress. Growing evidence has confirmed that H2-consumption exhibits preventive and therapeutic effects in patients with various diseases as well as model animals. Moreover, a small amount of H2 modulates signal transduction for regulating the expression of various genes; however, the primary target of H2 for exhibiting a variety of phenotypes was completely unknown. Here we show that H2 at low amounts manipulates oxidized phospholipid mediators to modulate Ca2+-signal transduction and gene expression.

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