Successful Reprogramming of Epiblast Stem Cells by Blocking Nuclear Localization of β-Catenin

Murayama, Hirokazu; Hara, Masaki; Sato, Hideyuki; Hayama, Toyoaki; Yamaguchi, Tomoyuki; Nakauchi, Hiromitsu

doi:10.1016/j.stemcr.2014.12.003

Cited by 31 publications

(32 citation statements)

References 33 publications

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“…These conclusions have been recently confirmed in mouse EpiSCs [94]. Further studies on reprogramming mouse EpiSCs to ES cells show that inhibition of Wnt/β-catenin signalling enhances the conversion [122]. …”

Section: Function Of Wnt/β-catenin Signalling In Embryonic and Epimentioning

confidence: 72%

Wnt/ß-catenin signalling and the dynamics of fate decisions in early mouse embryos and embryonic stem (ES) cells

Muñoz-Descalzo

Hadjantonakis

Arias

2015

Seminars in Cell & Developmental Biology

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Wnt/β-catenin signalling is a widespread cell signalling pathway with multiple roles during vertebrate development. In mouse embryonic stem (mES) cells, there is a dual role for β-catenin: it promotes differentiation when activated as part of the Wnt/β-catenin signalling pathway, and promotes stable pluripotency independently of signalling. Although mES cells resemble the preimplantation epiblast progenitors, the first requirement for Wnt/β-catenin signalling during mouse development has been reported at implantation [1,2]. The relationship between β-catenin and pluripotency and that of mES cells with epiblast progenitors suggests that β-catenin might have a functional role during preimplantation development. Here we summarize the expression and function of Wnt/β-catenin signalling elements during the early stages of mouse development and consider the reasons why the requirement in ES cells do not reflect the embryo.

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Section: Function Of Wnt/β-catenin Signalling In Embryonic and Epimentioning

confidence: 72%

Wnt/ß-catenin signalling and the dynamics of fate decisions in early mouse embryos and embryonic stem (ES) cells

Muñoz-Descalzo

Hadjantonakis

Arias

2015

Seminars in Cell & Developmental Biology

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“…The EpiSC line principally assayed was established from an EB3DR-injected chimeric E6.5 embryo as described (Murayama et al, 2015). EpiSC sub lines were subcloned by single-cell sorting from an established EpiSC line (Tesar et al, 2007).…”

Section: Preparation Of Mouse Episc Linesmentioning

confidence: 99%

Interspecific in vitro assay for the chimera-forming ability of human pluripotent stem cells

et al. 2015

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Functional assay limitations are an emerging issue in characterizing human pluripotent stem cells (PSCs). With rodent PSCs, chimera formation using pre-implantation embryos is the gold-standard assay of pluripotency (competence of progeny to differentiate into all three germ layers). In human PSCs (hPSCs), however, this can only be monitored via teratoma formation or in vitro differentiation, as ethical concerns preclude generation of human-human or human-animal chimeras. To circumvent this issue, we developed a functional assay utilizing interspecific blastocyst injection and in vitro culture (interspecies in vitro chimera assay) that enables the development and observation of embryos up to headfold stage. The assay uses mouse pre-implantation embryos and rat, monkey and human PSCs to create interspecies chimeras cultured in vitro to the early egg-cylinder stage. Intra-and interspecific chimera assays with rodent PSC lines were performed to confirm the consistency of results in vitro and in vivo. The behavior of chimeras developed in vitro appeared to recapitulate that of chimeras developed in vivo; that is, PSC-derived cells survived and were integrated into the epiblast of egg-cylinder-stage embryos. This indicates that the interspecific in vitro chimera assay is useful in evaluating the chimera-forming ability of rodent PSCs. However, when human induced PSCs (both conventional and naïve-like types) were injected into mouse embryos and cultured, some human cells survived but were segregated; unlike epiblast-stage rodent PSCs, they never integrated into the epiblast of egg-cylinder-stage embryos. These data suggest that the mouse-human interspecies in vitro chimera assay does not accurately reflect the early developmental potential/ process of hPSCs. The use of evolutionarily more closely related species as host embryos might be necessary to evaluate the developmental potency of hPSCs.

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“…In addition, the protein levels of OTX2, an important brain development transcription factor that is critical for ESC conversion into EpiSC (Acampora et al., 2013), are increased (Figure 2B). On the contrary, the protein levels of the essential naive state regulators NANOG, KLF4, and cadherin 1 (CDH1), recently reported to drive the transition from primed to naive pluripotency (Murayama et al., 2015), are sharply diminished (Figure 2B). Next, we verified that PML ablation negatively affects BMP4 signaling by reducing the activity of BRE-Luc reporter and the expression levels of its transcriptional targets Ids 1-3 (Figures 2C and 2D).…”

Section: Resultsmentioning

confidence: 99%

Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming

et al. 2017

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SummaryPromyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state. During differentiation of embryoid bodies, PML influences cell-fate decisions between mesoderm and endoderm by controlling the expression of Tbx3. PML loss compromises the reprogramming ability of embryonic fibroblasts to induced pluripotent stem cells by inhibiting the transforming growth factor β pathway at the very early stages. Collectively, these results designate PML as a member of the regulatory network for ESC naive pluripotency and somatic cell reprogramming.

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Successful Reprogramming of Epiblast Stem Cells by Blocking Nuclear Localization of β-Catenin

Cited by 31 publications

References 33 publications

Wnt/ß-catenin signalling and the dynamics of fate decisions in early mouse embryos and embryonic stem (ES) cells

Wnt/ß-catenin signalling and the dynamics of fate decisions in early mouse embryos and embryonic stem (ES) cells

Interspecific in vitro assay for the chimera-forming ability of human pluripotent stem cells

Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming

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