Successful Reprogramming of Epiblast Stem Cells by Blocking Nuclear Localization of β-Catenin
Autor: | Hideki Masaki, Hiromitsu Nakauchi, Tomonari Hayama, Hideyuki Murayama, Tomoyuki Yamaguchi, Hideyuki Sato |
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Rok vydání: | 2015 |
Předmět: |
Genetic Vectors
Clinical Sciences Gene Expression Germ layer Biology Leukemia Inhibitory Factor Biochemistry Article Cell Line Mice Gene Order Genetics Animals Induced pluripotent stem cell lcsh:QH301-705.5 Wnt Signaling Pathway beta Catenin Embryonic Stem Cells Cell Nucleus lcsh:R5-920 Stem Cells Gene Expression Profiling Wnt signaling pathway Cell Biology Cadherins Cellular Reprogramming Embryonic stem cell Rats Cell biology Protein Transport lcsh:Biology (General) Epiblast embryonic structures Female Biochemistry and Cell Biology Stem cell lcsh:Medicine (General) TCF Transcription Factors Leukemia inhibitory factor Reprogramming Germ Layers Signal Transduction Protein Binding Developmental Biology |
Zdroj: | Stem cell reports, vol 4, iss 1 Stem Cell Reports Stem Cell Reports, Vol 4, Iss 1, Pp 103-113 (2015) |
ISSN: | 2213-6711 |
Popis: | Summary Epiblast stem cells (EpiSCs) in mice and rats are primed pluripotent stem cells (PSCs). They barely contribute to chimeric embryos when injected into blastocysts. Reprogramming of EpiSCs to embryonic stem cell (ESC)-like cells (rESCs) may occur in response to LIF-STAT3 signaling; however, low reprogramming efficiency hampers potential use of rESCs in generating chimeras. Here, we describe dramatic improvement of conversion efficiency from primed to naive-like PSCs through upregulation of E-cadherin in the presence of the cytokine LIF. Analysis revealed that blocking nuclear localization of β-CATENIN with small-molecule inhibitors significantly enhances reprogramming efficiency of mouse EpiSCs. Although activation of Wnt/β-catenin signals has been thought desirable for maintenance of naive PSCs, this study provides the evidence that inhibition of nuclear translocation of β-CATENIN enhances conversion of mouse EpiSCs to naive-like PSCs (rESCs). This affords better understanding of gene regulatory circuits underlying pluripotency and reprogramming of PSCs. Highlights • E-cadherin overexpression considerably increases reprogramming efficiency of EpiSCs • E-cadherin overexpression negatively regulates β-catenin signaling in EpiSCs • Blocking nuclear localization of β-CATENIN enhances reprogramming of EpiSCs In this article, Nakauchi and colleagues show that dramatic improvement of conversion efficiency from primed to naive-like mouse pluripotent stem cells through blocking nuclear localization of β-CATENIN in the presence of the cytokine LIF. This affords better understanding of gene regulatory circuits underlying pluripotency and reprogramming of primed pluripotent stem cells. |
Databáze: | OpenAIRE |
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