An Intermediate Pluripotent State Controlled by MicroRNAs Is Required for the Naive-to-Primed Stem Cell Transition

Du, Peng; Pirouz, Mehdi; Choi, Jiho; Huebner, Aaron J.; Clement, Kendell; Meissner, Alexander; Hochedlinger, Konrad; Gregory, Richard I.

doi:10.1016/j.stem.2018.04.021

Cited by 51 publications

(38 citation statements)

References 50 publications

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“…To further compare the 5C‐Oct4GFP + cells with epiblast‐like cells (EpiLCs) and cells in formative state, previous reported datasets were downloaded and analyzed together with the current RNA‐Seq (Data ref: Hayashi et al , 2011; Data ref: Buecker, ; Data ref: Bertone, ; Data ref: Kalkan et al , ). Based on these datasets and previous reports (Hayashi et al , 2011; Kalkan et al , ; Smith, ; Du et al , ; Takahashi et al , ), cells in 5C state are quite different from EpiLCs and cells in formative state. Generally, cells in 5C state seldomly contributed to chimera and had high expression of glycolysis and mesenchymal markers (Fig EV3A).…”

Section: Resultssupporting

confidence: 56%

Metabolic switch and epithelial–mesenchymal transition cooperate to regulate pluripotency

et al. 2020

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Both metabolic switch from oxidative phosphorylation to glycolysis (OGS) and epithelial-mesenchymal transition (EMT) promote cellular reprogramming at early stages. However, their connections have not been elucidated. Here, when a chemically defined medium was used to induce early EMT during mouse reprogramming, a facilitated OGS was also observed at the same time. Additional investigations suggested that the two events formed a positive feedback loop via transcriptional activation, cooperated to upregulate epigenetic factors such as Bmi1, Ctcf, Ezh2, Kdm2b, and Wdr5, and accelerated pluripotency induction at the early stage. However, at late stages, by over-inducing glycolysis and preventing the necessary mesenchymal-epithelial transition, the two events trapped the cells at a new pluripotency state between naïve and primed states and inhibited further reprogramming toward the naïve state. In addition, the pluripotent stem cells at the new state have high similarity to epiblasts from E4.5 and E5.5 embryos, and have distinct characteristics from the previously reported epiblast-like or formative states. Therefore, the time-dependent cooperation between OGS and EMT in regulating pluripotency should extend our understanding of related fields.

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Section: Resultssupporting

confidence: 56%

Metabolic switch and epithelial–mesenchymal transition cooperate to regulate pluripotency

et al. 2020

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“…Those different phenotypes between dgcr8 −/− and dKO ESCs during the naïve-to-primed transition suggest other miRNAs also participate in this transition. Recently, a study by Du and colleagues demonstrated a protein involved in the biogenesis of polycistronic miRNAs (such as miR-17~92 ), Isy1, is necessary for the naïve-to-primed transition [196]. A set of miRNAs, including miR-17~92 and miR-290 , were up-regulated during the naïve-to-primed transition under the positive regulation of Isy1 [196].…”

Section: Functions Of Mirnas In Stem Cellsmentioning

confidence: 99%

Roles of MicroRNAs in Establishing and Modulating Stem Cell Potential

Zhang

Zhuang

Lin

2019

IJMS

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Early embryonic development in mammals, from fertilization to implantation, can be viewed as a process in which stem cells alternate between self-renewal and differentiation. During this process, the fates of stem cells in embryos are gradually specified, from the totipotent state, through the segregation of embryonic and extraembryonic lineages, to the molecular and cellular defined progenitors. Most of those stem cells with different potencies in vivo can be propagated in vitro and recapitulate their differentiation abilities. Complex and coordinated regulations, such as epigenetic reprogramming, maternal RNA clearance, transcriptional and translational landscape changes, as well as the signal transduction, are required for the proper development of early embryos. Accumulated studies suggest that Dicer-dependent noncoding RNAs, including microRNAs (miRNAs) and endogenous small-interfering RNAs (endo-siRNAs), are involved in those regulations and therefore modulate biological properties of stem cells in vitro and in vivo. Elucidating roles of these noncoding RNAs will give us a more comprehensive picture of mammalian embryonic development and enable us to modulate stem cell potencies. In this review, we will discuss roles of miRNAs in regulating the maintenance and cell fate potential of stem cells in/from mouse and human early embryos.

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“…As an example, ISY1 gene expression during the naive-to-primed ESC transition determines a specific phase of ‘poised’ pluripotency. ISY1 promotes exit from the naive state and is necessary and sufficient to induce and maintain balanced pluripotency; however, persistent ISY1 overexpression inhibits the exit from the naive to the primed state [ 114 ].…”

Section: Permanent Reontogenesis or Rejuvenation Circlementioning

confidence: 99%

From Cancer to Rejuvenation: Incomplete Regeneration as the Missing Link (Part II: Rejuvenation circle)

et al. 2020

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In the first part of our study, we substantiated that the embryonic reontogenesis and malignant growth (disintegrating growth) pathways are the same, but occur at different stages of ontogenesis, this mechanism is carried out in opposite directions. Cancer has been shown to be epigenetic-blocked redifferentiation and unfinished somatic embryogenesis. We formulated that only this approach of aging elimination has real prospects for a future that is fraught with cancer, as we will be able to convert this risk into a rejuvenation process through the continuous cycling of cell dedifferentiation–differentiation processes (permanent remorphogenesis). Here, we continue to develop the idea of looped ontogenesis and formulate the concept of the rejuvenation circle.

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An Intermediate Pluripotent State Controlled by MicroRNAs Is Required for the Naive-to-Primed Stem Cell Transition

Cited by 51 publications

References 50 publications

Metabolic switch and epithelial–mesenchymal transition cooperate to regulate pluripotency

Metabolic switch and epithelial–mesenchymal transition cooperate to regulate pluripotency

Roles of MicroRNAs in Establishing and Modulating Stem Cell Potential

From Cancer to Rejuvenation: Incomplete Regeneration as the Missing Link (Part II: Rejuvenation circle)

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