Molecular Control of Induced Pluripotency

Theunissen, Thorold W.; Jaenisch, Rudolf

doi:10.1016/j.stem.2014.05.002

Cited by 130 publications

(105 citation statements)

References 129 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This could be due to the time it took Brg1 and Baf155 to reach critical expression levels after retroviral transduction, causing them to act inefficiently during the critical window of intermediate reprogramming when transduced at later stages. These findings are consistent with previous conclusions showing that chromatin remodeling components act at an intermediate stage of reprogramming [2,13]. Interestingly, we found that Baf155 overexpression does not affect the pluripotency of hiPSCs.…”

Section: Discussionsupporting

confidence: 94%

“…Replacement by ME specifiers proposed the "seasaw model" of reprogramming mechanisms. In addition, depending on reprogramming factors using a "stochastic model, a deterministic model or a combination of both as well as a biphasic model" have been proposed to understand reprogramming mechanisms [13]. It has been shown that Oct4 deficient oocytes are capable of reprogramming somatic nuclei by somatic cell nuclear transfer (SCNT) with efficiency similar to normal oocytes [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

BAF Complex Enhances Reprogramming of Adult Human Fibroblasts

Singhal¹,

Araúzo-Bravo²,

Sinn³

et al. 2016

J Stem Cell Res Ther

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

BAF Complex Enhances Reprogramming of Adult Human Fibroblasts

Singhal¹,

Araúzo-Bravo²,

Sinn³

et al. 2016

J Stem Cell Res Ther

View full text Add to dashboard Cite

“…1 In studying aspects of somatic cell reprogramming related to pluripotency, dramatic and complex molecular changes at the genetic, epigenetic, and metabolic levels have been observed during the initial stage of reprogramming. 2 Cell reprogramming faces the challenge of balancing stability and plasticity and must overcome critical barriers, such as cell cycle checkpoints, the mesenchymal-epithelial transition, and metabolic reprogramming, to progress cell fate conversion from a stochastic early phase toward pluripotency. 3 The p53 pathway limits cell fate transition by inducing classical signaling that leads to cell cycle arrest, senescence, or apoptosis to maintain genome stability in the face of reprogramming-induced stress.…”

mentioning

confidence: 99%

Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency

et al. 2015

View full text Add to dashboard Cite

Cell reprogramming technology has allowed the in vitro control of cell fate transition, thus allowing for the generation of highly desired cell types to recapitulate in vivo developmental processes and architectures. However, the precise molecular mechanisms underlying the reprogramming process remain to be defined. Here, we show that depleting p53 and p21, which are barriers to reprogramming, yields a high reprogramming efficiency. Deletion of these factors results in a distinct mitochondrial background with low expression of oxidative phosphorylation subunits and mitochondrial fusion proteins, including mitofusin 1 and 2 (Mfn1/2). Importantly, Mfn1/2 depletion reciprocally inhibits the p53-p21 pathway and promotes both the conversion of somatic cells to a pluripotent state and the maintenance of pluripotency. Mfn1/2 depletion facilitates the glycolytic metabolic transition through the activation of the Ras-Raf and hypoxia-inducible factor 1α (HIF1α) signaling at an early stage of reprogramming. HIF1α is required for increased glycolysis and reprogramming by Mfn1/2 depletion. Taken together, these results demonstrate that Mfn1/2 constitutes a new barrier to reprogramming, and that Mfn1/2 ablation facilitates the induction of pluripotency through the restructuring of mitochondrial dynamics and bioenergetics. Cell Death and Differentiation (2015) 22, 1957-1969 doi:10.1038/cdd.2015; published online 17 April 2015Cell fate transition occurs under various developmental, physiological, and pathological conditions, including normal embryonic development, aging, and tissue regeneration, as well as tumor initiation and progression. Defining the cellular and molecular mechanisms of cell fate transition and learning to control these mechanisms may be essential for treating abnormal pathological conditions resulting from improper regulation of cell fate. The recent development of induced pluripotent stem cell (iPSC) technology has allowed for the reprogramming of somatic cells to pluripotent stem cells through the use of defined pluripotency factors, and has allowed us to more closely mimic and recapitulate the conditions of cell fate transitions.1 In studying aspects of somatic cell reprogramming related to pluripotency, dramatic and complex molecular changes at the genetic, epigenetic, and metabolic levels have been observed during the initial stage of reprogramming.2 Cell reprogramming faces the challenge of balancing stability and plasticity and must overcome critical barriers, such as cell cycle checkpoints, the mesenchymal-epithelial transition, and metabolic reprogramming, to progress cell fate conversion from a stochastic early phase toward pluripotency. 3The p53 pathway limits cell fate transition by inducing classical signaling that leads to cell cycle arrest, senescence, or apoptosis to maintain genome stability in the face of reprogramming-induced stress. Thus, compromising p53 signaling accelerates the reprogramming process.4-6 Recent reports have provided data showing that the fast-cycling population is enric...

show abstract

“…In addition, interference with DNMT1 promotes iPSC formation, also supporting that DNA methylation is a feature limiting reprogramming to pluripotency [101] . All reprogramming techniques involve demethylation of the genome thus appearing as a crucial process for successfully achieving pluripotency [120,121] .…”

Section: Reprogramming Factors and Epigenetic Mechanismsmentioning

confidence: 99%

Epigenetic regulation of stemness maintenance in the neurogenic niches

Montalbán-Loro

Domingo-Muelas

Bizy

et al. 2015

WJSC

View full text Add to dashboard Cite

In the adult mouse brain, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are two zones that contain neural stem cells (NSCs) with the capacity to give rise to neurons and glia during the entire life of the animal. Spatial and temporal regulation of gene expression in the NSCs population is established and maintained by the coordinated interaction between transcription factors and epigenetic regulators which control stem cell fate. Epigenetic mechanisms are heritable alterations in genome function that do not involve changes in DNA sequence itself but that modulate gene expression, acting as mediators between the environment and the genome. At the molecular level, those epigenetic mechanisms comprise chemical modifications of DNA such as methylation, hydroxymethylation and histone modifications needed for the maintenance of NSC identity. Genomic imprinting is another normal epigenetic process leading to parentalspecific expression of a gene, known to be implicated in the control of gene dosage in the neurogenic niches. The generation of induced pluripotent stem cells from NSCs by expression of defined transcription factors, provide key insights into fundamental principles of stem cell biology. Epigenetic modifications can also occur during reprogramming of NSCs to pluripotency and a better understanding of this process will help to elucidate the mechanisms required for stem cell maintenance. This review takes advantage of recent studies from the epigenetic field to report knowledge regarding the mechanisms of stemness maintenance of neural stem cells in the neurogenic niches.

show abstract

Molecular Control of Induced Pluripotency

Cited by 130 publications

References 129 publications

BAF Complex Enhances Reprogramming of Adult Human Fibroblasts

BAF Complex Enhances Reprogramming of Adult Human Fibroblasts

Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency

Epigenetic regulation of stemness maintenance in the neurogenic niches

Contact Info

Product

Resources

About