The role of prion protein in stem cell regulation

Miranda, Alberto; Ramos‐Ibeas, Priscila; Pericuesta, Eva; Ramírez, Miguel Ángel; Gutiérrez‐Adán, Alfonso

doi:10.1530/rep-13-0100

Cited by 18 publications

(16 citation statements)

References 81 publications

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“…In fact, although highly concentrated within the CNS, this membrane-bound extracellular glycoprotein, is ubiquitous in humans and extremely conserved throughout the evolution. In this context, several studies proposed that PrP C is involved in the regulation of stem cell self-renewal, proliferation and differentiation [64, 65]. Moreover, more recently it was suggested that PrP C might also promote human tumor development and diffusion, and the induction of drug resistance [22, 36].…”

Section: Discussionmentioning

confidence: 99%

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

et al. 2016

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Prion protein (PrPC) is a cell surface glycoprotein whose misfolding is responsible for prion diseases. Although its physiological role is not completely defined, several lines of evidence propose that PrPC is involved in self-renewal, pluripotency gene expression, proliferation and differentiation of neural stem cells. Moreover, PrPC regulates different biological functions in human tumors, including glioblastoma (GBM). We analyzed the role of PrPC in GBM cell pathogenicity focusing on tumor-initiating cells (TICs, or cancer stem cells, CSCs), the subpopulation responsible for development, progression and recurrence of most malignancies. Analyzing four GBM CSC-enriched cultures, we show that PrPC expression is directly correlated with the proliferation rate of the cells. To better define its role in CSC biology, we knocked-down PrPC expression in two of these GBM-derived CSC cultures by specific lentiviral-delivered shRNAs. We provide evidence that CSC proliferation rate, spherogenesis and in vivo tumorigenicity are significantly inhibited in PrPC down-regulated cells. Moreover, PrPC down-regulation caused loss of expression of the stemness and self-renewal markers (NANOG, Sox2) and the activation of differentiation pathways (i.e. increased GFAP expression). Our results suggest that PrPC controls the stemness properties of human GBM CSCs and that its down-regulation induces the acquisition of a more differentiated and less oncogenic phenotype.

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Section: Discussionmentioning

confidence: 99%

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

et al. 2016

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“…Notably, early developmental arrests were described in PrP knock out models of zebrafish 9 supporting the role of PrP C in early development in at least one taxonomic class. The recent article by Miranda et al provides comprehensive review of the studies on the role of PrP C in stem cell pluripotency, self-renewal and differentiation, 53 therefore we will only discuss the results that are the most relevant to the current finding. During early embryogenesis, PrP C expression was found to be largely limited to cells that undergo neural differentiation.…”

Section: Discussionmentioning

confidence: 99%

The cellular form of the prion protein guides the differentiation of human embryonic stem cells into neuron-, oligodendrocyte-, and astrocyte-committed lineages

Lee

Baskakov

2014

Prion

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Prion protein, PrP C , is a glycoprotein that is expressed on the cell surface beginning with the early stages of embryonic stem cell differentiation. Previously, we showed that ectopic expression of PrP C in human embryonic stem cells (hESCs) triggered differentiation toward endodermal, mesodermal, and ectodermal lineages, whereas silencing of PrP C suppressed differentiation toward ectodermal but not endodermal or mesodermal lineages. Considering that PrP C might be involved in controlling the balance between cells of different lineages, the current study was designed to test whether PrP C controls differentiation of hESCs into cells of neuron-, oligodendrocyte-, and astrocyte-committed lineages. PrP C was silenced in hESCs cultured under three sets of conditions that were previously shown to induce hESCs differentiation into predominantly neuron-, oligodendrocyte-, and astrocyte-committed lineages. We found that silencing of PrP C suppressed differentiation toward all three lineages. Similar results were observed in all three protocols, arguing that the effect of PrP C was independent of differentiation conditions employed. Moreover, switching PrP C expression during a differentiation time course revealed that silencing PrP C expression during the very initial stage that corresponds to embryonic bodies has a more significant impact than silencing at later stages of differentiation. The current work illustrates that PrP C controls differentiation of hESCs toward neuron-, oligodendrocyte-, and astrocytecommitted lineages and is likely involved at the stage of uncommitted neural progenitor cells rather than lineagecommitted neural progenitors.

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“…Mammalian prions share many common features with their counterparts in yeast, but their function and patterns of inheritance are less well known. Nevertheless, they have been shown to regulate pluripotency in mouse embryonic cells and contribute to their differentiation into neural progenitor cells (Peralta et al 2011;Miranda et al 2013). Importantly, normal PrP (PrP C ) are also present in bovine oocytes and pre-elongation embryos (Peralta et al 2012), although again their function is poorly understood.…”

Section: Inter(trans)generational Inheritancementioning

confidence: 99%

Epigenetics and developmental programming of welfare and production traits in farm animals

Sinclair

Rutherford

Wallace

et al. 2016

Reprod. Fertil. Dev.

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Abstract. The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

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The role of prion protein in stem cell regulation

Cited by 18 publications

References 81 publications

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

Cellular prion protein controls stem cell-like properties of human glioblastoma tumor-initiating cells

The cellular form of the prion protein guides the differentiation of human embryonic stem cells into neuron-, oligodendrocyte-, and astrocyte-committed lineages

Epigenetics and developmental programming of welfare and production traits in farm animals

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