Role of the epithelial–mesenchymal transition and its effects on embryonic stem cells

Kim, Yeseul; Yi, Bo‐Rim; Kim, Nam‐Hyung; Choi, Kyung‐Chul

doi:10.1038/emm.2014.44

Cited by 103 publications

(94 citation statements)

References 62 publications

(95 reference statements)

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“…S3I-V), including the activating transcription factor ZEB1 and the induced mesenchymal marker vimentin (Kim et al, 2014). This is consistent with animal studies in which EMT underpins the migration of EPDCs into the subepicardial layer, prior to contributing derivatives to the developing coronary arteries and interstitial fibroblasts (Sylva et al, 2014).…”

Section: Resultssupporting

confidence: 73%

Characterisation of the human embryonic and foetal epicardium during heart development

Risebro¹,

Vieira

Klotz³

et al. 2015

Development

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The epicardium is essential for mammalian heart development. At present, our understanding of the timing and morphogenetic events leading to the formation of the human epicardium has essentially been extrapolated from model organisms. Here, we studied primary tissue samples to characterise human epicardium development. We reveal that the epicardium begins to envelop the myocardial surface at Carnegie stage (CS) 11 and this process is completed by CS15, earlier than previously inferred from avian studies. Contrary to prevailing dogma, the formed human epicardium is not a simple squamous epithelium and we reveal evidence of more complex structure, including novel spatial differences aligned to the developing chambers. Specifically, the ventricular, but not atrial, epicardium exhibited areas of expanded epithelium, preferential cell alignment and spindle-like morphology. Likewise, we reveal distinct properties ex vivo, such that ventricular cells spontaneously differentiate and lose epicardial identity, whereas atrial-derived cells remained 'epithelial-like'. These data provide insight into the developing human epicardium that may contribute to our understanding of congenital heart disease and have implications for the development of strategies for endogenous cell-based cardiac repair.

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Section: Resultssupporting

confidence: 73%

Characterisation of the human embryonic and foetal epicardium during heart development

Risebro¹,

Vieira

Klotz³

et al. 2015

Development

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“…For comprehensive review, refer to Kalluri andWeinberg (2009), Thiery et al (2009) and Peinado et al (2007). hESC were suggested to undergo EMT during cell differentiation; however, the underlying mechanism is not that much studied as compared to EMT in embryonic development and cancer (Kim et al 2014). Early studies revealed that cultivation of hESC on extracellular matrix-coated plates and fibroblast-conditioned medium results in morphological changes at the periphery of the colonies.…”

Section: Epithelial-to-mesenchymal Transition Differentiation and Stmentioning

confidence: 99%

Full biological characterization of human pluripotent stem cells will open the door to translational research

et al. 2016

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Since the discovery of human embryonic stem cells (hESC) and human-induced pluripotent stem cells (hiPSC), great hopes were held for their therapeutic application including disease modeling, drug discovery screenings, toxicological screenings and regenerative therapy. hESC and hiPSC have the advantage of indefinite self-renewal, thereby generating an inexhaustible pool of cells with, e.g., specific genotype for developing putative treatments; they can differentiate into derivatives of all three germ layers enabling autologous transplantation, and via donor-selection they can express various genotypes of interest for better disease modeling. Furthermore, drug screenings and toxicological screenings in hESC and hiPSC are more pertinent to identify drugs or chemical compounds that are harmful for human, than a mouse model could predict. Despite continuing research in the wide field of therapeutic applications, further understanding of the underlying basic mechanisms of stem cell function is necessary. Here, we summarize current knowledge concerning pluripotency, self-renewal, apoptosis, motility, epithelial-to-mesenchymal transition and differentiation of pluripotent stem cells.

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“…It has been well established that during their pluripotent state, mESCs express high levels of cell adhesion proteins, most prominently E-cadherins [5][6][7]. This is unsurprising as preliminary formation of the ICM is heavily dependent on cell-cell interactions that dynamically form the physical properties of their microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Physical confinement signals regulate the organization of stem cells in three dimensions

Hadjiantoniou

Sibrac

Ignacio

et al. 2016

J. R. Soc. Interface.

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During embryogenesis, the spherical inner cell mass (ICM) proliferates in the confined environment of a blastocyst. Embryonic stem cells (ESCs) are derived from the ICM, and mimicking embryogenesis in vitro, mouse ESCs (mESCs) are often cultured in hanging droplets. This promotes the formation of a spheroid as the cells sediment and aggregate owing to increased physical confinement and cell-cell interactions. In contrast, mESCs form two-dimensional monolayers on flat substrates and it remains unclear if the difference in organization is owing to a lack of physical confinement or increased cell-substrate versus cell-cell interactions. Employing microfabricated substrates, we demonstrate that a single geometric degree of physical confinement on a surface can also initiate spherogenesis. Experiment and computation reveal that a balance between cell-cell and cell-substrate interactions finely controls the morphology and organization of mESC aggregates. Physical confinement is thus an important regulatory cue in the three-dimensional organization and morphogenesis of developing cells.

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Role of the epithelial–mesenchymal transition and its effects on embryonic stem cells

Cited by 103 publications

References 62 publications

Characterisation of the human embryonic and foetal epicardium during heart development

Characterisation of the human embryonic and foetal epicardium during heart development

Full biological characterization of human pluripotent stem cells will open the door to translational research

Physical confinement signals regulate the organization of stem cells in three dimensions

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