OCT4: Less is more

Wagner, Ryan T.; Cooney, Austin J.

doi:10.1038/cr.2009.48

Cited by 9 publications

(4 citation statements)

References 14 publications

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“…The most prominent feature consisted of a complete absence of the Nanog protein at the end of the differentiation interval (4 weeks). We speculate that Nanog This finding is in agreement with the mutual regulatory circuit settled by these two genes in ESC [36][37][38]. Surprisingly, the observed decline …”

Section: Translational Neurosciencesupporting

confidence: 78%

Expression analysis of pluripotency-associated genes in human fetal cortical and striatal neural stem cells during differentiation

Massa

Pillai

Monni

et al. 2012

Translational Neuroscience

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In the field of developmental biology, there is compelling evidence for a network of activity of pluripotency and stem-associated genes comprising of Oct4, Nanog and nestin. During neurogenesis, the choice between enhancement versus suppression of transcriptional modulation of these identified genes determines the balance between self-renewal neural stem cells (NSC) and immature neuronal phenotypes. By using immunocytochemistry and RT-PCR techniques, our study aims to address the question whether and to what extent mRNA and protein profiles are expressed in human fetal neurospheres obtained from cortical and striatal brain regions, both in expansion (undifferentiated cells) and differentiation conditions monitored after 1 and 4 weeks in vitro culturing. Our results clearly demonstrate the sustained presence of opposite signals: strong downregulation of Oct4 and Nanog genes in cortical differentiating cells and significant up-regulation for nestin gene both in cortical and striatal differentiating cells. Notably, by immunostaining techniques, Oct4 and Nanog protein expression have indicated the presence of both nuclear and cytoplasmic content followed by their rapid turnover (immediately after 1 week). Moreover, during the differentiation process, dissociated neurospheres displayed unexpected number of nestin positive cells accompanied by a constant level of staining intensity. In conclusion, the present study provides new insights into brain region related features in terms of Oct4, Nanog and nestin expression both at cellular and molecular level.

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Section: Translational Neurosciencesupporting

confidence: 78%

Expression analysis of pluripotency-associated genes in human fetal cortical and striatal neural stem cells during differentiation

Massa

Pillai

Monni

et al. 2012

Translational Neuroscience

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“…Although our data suggested that Oct4 was predominantly localized to the cytoplasm, it was not excluded from the nucleus, so a functional role as a transcription factor remains possible. It may not be surprising that Oct4 protein is hard to detect despite significant levels of its transcript, as Oct4 protein has been shown to be processed by ubiquitination and rapidly turned over (Saxe et al., 2009; Wagner & Cooney, 2009).…”

Section: Discussionmentioning

confidence: 99%

Dynamic methylation and expression of Oct4 in early neural stem cells

et al. 2010

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Neural stem cells are a multipotent population of tissue-specific stem cells with a broad but limited differentiation potential. However, recent studies have shown that over-expression of the pluripotency gene, Oct4, alone is sufficient to initiate a process by which these can form 'induced pluripotent stem cells' (iPS cells) with the same broad potential as embryonic stem cells. This led us to examine the expression of Oct4 in endogenous neural stem cells, as data regarding its expression in neural stem cells in vivo are contradictory and incomplete. In this study we have therefore analysed the expression of Oct4 and other genes associated with pluripotency throughout development of the mouse CNS and in neural stem cells grown in vitro. We find that Oct4 is still expressed in the CNS by E8.5, but that this expression declines rapidly until it is undetectable by E15.5. This decline is coincident with the gradual methylation of the Oct4 promoter and proximal enhancer. Immunostaining suggests that the Oct4 protein is predominantly cytoplasmic in location. We also found that neural stem cells from all ages expressed the pluripotency associated genes, Sox2, c-Myc, Klf4 and Nanog. These data provide an explanation for the varying behaviour of cells from the early neuroepithelium at different stages of development. The expression of these genes also provides an indication of why Oct4 alone is sufficient to induce iPS formation in neural stem cells at later stages.

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“…There are two possible explanations for the Oct4 expressional loss: 1, many pluripotent genes including Oct4 gene have their autoregulatory loops and their proteins degradation is strictly regulated in a self-dosage-dependent manner (Liao & Jin, 2010;Wagner & Cooney, 2009). Therefore, first possibility considered by us is that porcine OCT4 is shut down because that in fused cell, the whole amount of Oct4 transcription (mouse ES cell-origin Oct4 plus porcine KO cell-origin OCT4) is too much and exceeds the upper threshold at the early stage of fusion.…”

Section: Discussionmentioning

confidence: 99%

Interspecies cell fusion between mouse embryonic stem cell and porcine pluripotent cell

Bou

Guo

Fang

et al. 2021

Reprod Domestic Animals

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Cell reprogramming can change the fate of differentiated cells because their cell memory can be erased and new characters and functions are obtained relying on both global transcriptome and epigenetic changes. At present, we can reprogram differentiated cells into a pluripotent state by various methods including somatic cell nuclear transfer (SCNT), induction of pluripotency by defined factors (iPS) and cell fusion with pluripotent cells. SCNT (Wilmut et al., 1997) refers to reprogramming nucleus to pluripotent state by transferring a differentiated cell nucleus to an enucleated oocyte or early embryos. Yamanaka (Takahashi & Yamanaka, 2006) showed that lentiviral-induced expression of transcription factors Oct4, Sox2, c-Myc and Klf-4 in mouse somatic cells could turn cells into pluripotent state. In addition, small molecules can also be used to reprogram somatic cells. These resultant cells are termed chemically induced pluripotent stem (ciPS) cells and display similar morphological and physiological characteristics, differentiation potential and global gene expression profiles, with traditional iPS cells and ES cells (Hou et al., 2013).Cell fusion experiments that began 50 years ago were used to fuse cells of same types to formhomokaryons, or used to fuse

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OCT4: Less is more

Cited by 9 publications

References 14 publications

Expression analysis of pluripotency-associated genes in human fetal cortical and striatal neural stem cells during differentiation

Expression analysis of pluripotency-associated genes in human fetal cortical and striatal neural stem cells during differentiation

Dynamic methylation and expression of Oct4 in early neural stem cells

Interspecies cell fusion between mouse embryonic stem cell and porcine pluripotent cell

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