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Dive into the research topics where Virginie Sottile is active.

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Featured researches published by Virginie Sottile.


Cloning and Stem Cells | 2003

In vitro osteogenic differentiation of human ES cells.

Virginie Sottile; Alison J. Thomson; Jim McWhir

Since their isolation in 1998, human embryonic stem (hES) cells have been shown to be capable of adopting various cell fates in vitro. Here, we present in vitro data demonstrating the directed commitment of human embryonic stem cells to the osteogenic lineage. Human ES cells are shown to respond to factors that promote osteogenesis, leading to activation of the osteogenic markers osteocalcin, parathyroid hormone receptor, bone sialoprotein, osteopontin, cbfa1, and collagen 1. Moreover, the mineralized nodules obtained are composed of hydroxyapatite, further establishing the similarity of osteoblasts in culture to bone. These results show that osteoblasts can be derived from human ES cultures in vitro and provide the basis for comparison of adult and embryonic-derived osteogenesis, and for an investigation of potential applications for hES cells in orthopaedic tissue repair.


Stem Cells | 2004

Immortalized Fibroblast‐Like Cells Derived from Human Embryonic Stem Cells Support Undifferentiated Cell Growth

Chunhui Xu; Jianjie Jiang; Virginie Sottile; Jim McWhir; Jane Lebkowski; Melissa K. Carpenter

Human embryonic stem cells (hESCs) have the potential to generate multiple cell types and hold promise for future therapeutic applications. Although undifferentiated hESCs can proliferate indefinitely, hESC derivatives significantly downregulate telomerase and have limited replication potential. In this study we examine whether the replicative lifespan of hESC derivatives can be extended by ectopic expression of human telomerase reverse transcriptase (hTERT), the catalytic component of the telomerase complex. To this end, we have derived HEF1 cells, a fibroblast‐like cell type, differentiated from hESCs. Infection of HEF1 cells with a retrovirus expressing hTERT extends their replicative capacity, resulting in immortal human HEF1‐hTERT cells. HEF1‐hTERT cells can be used to produce conditioned medium (CM) capable of supporting hESC growth under feeder‐free conditions. Cultures maintained in HEF1‐CM show characteristics similar to mouse embryonic fibroblast CM control cultures, including morphology, surface marker and transcription factor expression, telomerase activity, differentiation, and karyotypic stability. In addition, HEF1‐hTERT cells have the capacity to differentiate into cells of the osteogenic lineage. These results suggest that immortalized cell lines can be generated from hESCs and that cells derived from hESCs can be used to support their own growth, creating a genotypically homogeneous system for the culture of hESCs.


Journal of Postgraduate Medicine | 2007

Adult mesenchymal stem cells: Differentiation potential and therapeutic applications

Leigh Jackson; Jones; Paul J. Scotting; Virginie Sottile

Adult mesenchymal stem cells (MSCs) are a population of multipotent cells found primarily in the bone marrow. They have long been known to be capable of osteogenic, adipogenic and chondrogenic differentiation and are currently the subject of a number of trials to assess their potential use in the clinic. Recently, the plasticity of these cells has come under close scrutiny as it has been suggested that they may have a differentiation potential beyond the mesenchymal lineage. Myogenic and in particular cardiomyogenic potential has been shown in vitro. MSCs have also been shown to have the ability to form neural cells both in vitro and in vivo, although the molecular mechanisms underlying these apparent transdifferentiation events are yet to be elucidated. We describe here the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for future applications in regenerative medicine.


FEBS Letters | 2000

Bone morphogenetic protein-2 stimulates adipogenic differentiation of mesenchymal precursor cells in synergy with BRL 49653 (rosiglitazone)

Virginie Sottile; Klaus Seuwen

Bone morphogenetic proteins (BMPs) were discovered as potent bone‐inducing molecules. Their effect on adipogenic differentiation is not well understood, both stimulation and inhibition of the process have been described. We show here that BMP‐2 strongly stimulates adipogenic differentiation of murine 3T3‐L1 preadipocytes if applied together with an agonist of peroxisome proliferator‐activated receptor γ (PPARγ). On its own, BMP‐2 (500 ng/ml) did not stimulate adipogenesis as quantified by flow cytometry with the lipophilic dye Nile Red. However, the protein strongly potentiated adipogenesis stimulated by the thiazolidinedione BRL 49653 as well as glycerol‐3‐phosphate dehydrogenase activity and induction of mRNAs for the adipogenic markers PPARγ and adipsin. We confirmed the synergistic action of BMP‐2 and BRL 49653 with primary cultures of rat bone marrow stromal cells. Our data demonstrate that BMP‐2 can act as a potent adipogenic agent if presented together with activators of PPARγ.


Brain Research | 2006

Stem cell marker expression in the Bergmann glia population of the adult mouse brain

Virginie Sottile; Meng Li; Paul J. Scotting

Recent evidence suggests that the postnatal cerebellum contains cells with characteristics of neural stem cells, which had so far only been identified in the subventricular zone of the lateral ventricles and the subdentate gyrus of the hippocampus. In order to investigate the identity of these cells in the adult cerebellum, we have analyzed the expression of Sox1, a transcription factor from the SoxB1 subgroup and widely used marker of neural stem cells. In situ hybridization and the use of a transgenic mouse model show that, in the adult cerebellum, Sox 1 is only expressed in the Bergmann glia, a population of radial glia present in the Purkinje cell layer. Furthermore, another neural stem cell marker, Sox2 (also member of the SoxB1 subgroup), is also expressed in the Bergmann glia. We have previously shown that these same cells express Sox9, a member of the SoxE subgroup known for its role in glial development. Here we show that Sox9 is in fact also expressed in other regions harboring adult neural stem cells, suggesting that Sox9 represents a novel stem cell marker. Finally, using a Sox1-null mouse, we show that the formation of this Sox2/Sox9 positive Bergmann glia population does not require the presence of a functional Sox1. Our results identify these radial glia as a previously unreported Sox1/Sox2/Sox9 positive adult cell population, suggesting that these cells may represent the recently reported stem cells in the adult cerebellum.


Analytical Chemistry | 2012

Cytoplasmic RNA in Undifferentiated Neural Stem Cells: A Potential Label-Free Raman Spectral Marker for Assessing the Undifferentiated Status

Adrian Ghita; Flavius C. Pascut; Melissa L. Mather; Virginie Sottile; Ioan Notingher

Raman microspectroscopy (rms) was used to identify, image, and quantify potential molecular markers for label-free monitoring the differentiation status of live neural stem cells (NSCs) in vitro. Label-free noninvasive techniques for characterization of NCSs in vitro are needed as they can be developed for real-time monitoring of live cells. Principal component analysis (PCA) and linear discriminant analysis (LDA) models based on Raman spectra of undifferentiated NSCs and NSC-derived glial cells enabled discrimination of NSCs with 89.4% sensitivity and 96.4% specificity. The differences between Raman spectra of NSCs and glial cells indicated that the discrimination of the NSCs was based on higher concentration of nucleic acids in NSCs. Spectral images corresponding to Raman bands assigned to nucleic acids for individual NSCs and glial cells were compared with fluorescence staining of cell nuclei and cytoplasm to show that the origin of the spectral differences were related to cytoplasmic RNA. On the basis of calibration models, the concentration of the RNA was quantified and mapped in individual cells at a resolution of ~700 nm. The spectral maps revealed cytoplasmic regions with concentrations of RNA as high as 4 mg/mL for NSCs while the RNA concentration in the cytoplasm of the glial cells was below the detection limit of our instrument (~1 mg/mL). In the light of recent reports describing the importance of the RNAs in stem cell populations, we propose that the observed high concentration of cytoplasmic RNAs in NSCs compared to glial cells is related to the repressed translation of mRNAs, higher concentrations of large noncoding RNAs in the cytoplasm as well as their lower cytoplasm volume. While this study demonstrates the potential of using rms for label-free assessment of live NSCs in vitro, further studies are required to establish the exact origin of the increased contribution of the cytoplasmic RNA.


BioEssays | 2009

The chick embryo: hatching a model for contemporary biomedical research.

Hassan Rashidi; Virginie Sottile

Animal models play a crucial role in fundamental and medical research. Progress in the fields of drug discovery, regenerative medicine and cancer research among others are heavily dependent on in vivo models to validate in vitro observations, and develop new therapeutic approaches. However, conventional rodent and large animal experiments face ethical, practical and technical issues that limit their usage. The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology, gene expression analysis and loss/gain of function experiments. It is also an established model for tissue/cell transplantation, and because of its lack of immune system in early development, the chick embryo is increasingly recognised as a model of choice for mammalian biology with new applications for stem cell and cancer research. Here, we review novel applications of the chick embryo model, and discuss future developments of this in vivo model for biomedical research.


Development | 2010

Axolotl Nanog activity in mouse embryonic stem cells demonstrates that ground state pluripotency is conserved from urodele amphibians to mammals

James E. Dixon; Cinzia Allegrucci; Catherine Redwood; Kevin Kump; Yuhong Bian; Jodie Chatfield; Yi-Hsien Chen; Virginie Sottile; S. Randal Voss; Ramiro Alberio; Andrew D. Johnson

Cells in the pluripotent ground state can give rise to somatic cells and germ cells, and the acquisition of pluripotency is dependent on the expression of Nanog. Pluripotency is conserved in the primitive ectoderm of embryos from mammals and urodele amphibians, and here we report the isolation of a Nanog ortholog from axolotls (axNanog). axNanog does not contain a tryptophan repeat domain and is expressed as a monomer in the axolotl animal cap. The monomeric form is sufficient to regulate pluripotency in mouse embryonic stem cells, but axNanog dimers are required to rescue LIF-independent self-renewal. Our results show that protein interactions mediated by Nanog dimerization promote proliferation. More importantly, they demonstrate that the mechanisms governing pluripotency are conserved from urodele amphibians to mammals.


Molecular Cancer | 2011

Epigenetic reprogramming of breast cancer cells with oocyte extracts

Cinzia Allegrucci; Michael D Rushton; James E. Dixon; Virginie Sottile; Mansi Shah; Rajendra Kumari; Sue Watson; Ramiro Alberio; Andrew D. Johnson

BackgroundBreast cancer is a disease characterised by both genetic and epigenetic alterations. Epigenetic silencing of tumour suppressor genes is an early event in breast carcinogenesis and reversion of gene silencing by epigenetic reprogramming can provide clues to the mechanisms responsible for tumour initiation and progression. In this study we apply the reprogramming capacity of oocytes to cancer cells in order to study breast oncogenesis.ResultsWe show that breast cancer cells can be directly reprogrammed by amphibian oocyte extracts. The reprogramming effect, after six hours of treatment, in the absence of DNA replication, includes DNA demethylation and removal of repressive histone marks at the promoters of tumour suppressor genes; also, expression of the silenced genes is re-activated in response to treatment. This activity is specific to oocytes as it is not elicited by extracts from ovulated eggs, and is present at very limited levels in extracts from mouse embryonic stem cells. Epigenetic reprogramming in oocyte extracts results in reduction of cancer cell growth under anchorage independent conditions and a reduction in tumour growth in mouse xenografts.ConclusionsThis study presents a new method to investigate tumour reversion by epigenetic reprogramming. After testing extracts from different sources, we found that axolotl oocyte extracts possess superior reprogramming ability, which reverses epigenetic silencing of tumour suppressor genes and tumorigenicity of breast cancer cells in a mouse xenograft model. Therefore this system can be extremely valuable for dissecting the mechanisms involved in tumour suppressor gene silencing and identifying molecular activities capable of arresting tumour growth. These applications can ultimately shed light on the contribution of epigenetic alterations in breast cancer and advance the development of epigenetic therapies.


Cell Research | 2009

Dynamic distribution and stem cell characteristics of Sox1-expressing cells in the cerebellar cortex

Joelle Alcock; Virginie Sottile

Bergmann glia cells are a discrete radial glia population surrounding Purkinje cells in the cerebellar cortex. Although Bergmann glia are essential for the development and correct arborization of Purkinje cells, little is known about the regulation of this cell population after the developmental phase. In an effort to characterize this population at the molecular level, we have analyzed marker expression and established that adult Bergmann glia express Sox1, Sox2 and Sox9, a feature otherwise associated with neural stem cells (NSCs). In the present study, we have further analyzed the developmental pattern of Sox1-expressing cells in the developing cerebellum. We report that before becoming restricted to the Purkinje cell layer, Sox1-positive cells are present throughout the immature tissue, and that these cells show characteristics of Bergmann glia progenitors. Our study shows that these progenitors express Sox1, Sox2 and Sox9, a signature maintained throughout cerebellar maturation into adulthood. When isolated in culture, the Sox1-expressing cerebellar population exhibited neurosphere-forming ability, NSC-marker characteristics, and demonstrated multipotency at the clonal level. Our results show that the Bergmann glia population expresses Sox1 during cerebellar development, and that these cells can be isolated and show stem cell characteristics in vitro, suggesting that they could hold a broader potential than previously thought.

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David M. Grant

University of Nottingham

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Ifty Ahmed

University of Nottingham

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Chris Denning

University of Nottingham

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Ioan Notingher

University of Nottingham

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