Transduction of neural stem cells with oncogenes
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Transduction of neural stem cells with oncogenes a novel model for the study of brain tumorigenesis. by Victoria Elizabeth Bonn

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Published .
Written in English


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The cell of origin of brain tumours is unknown and determinants of brain tumour phenotype are poorly understood. Evidence suggests a neural stem cell is the target for transformation leading to a brain tumour. In this thesis, we established a model system to test whether neural stem cells may be transformed and driven down a particular differentiation pathway. Neural stem cells, cultured as neurospheres, were retrovirally infected in vitro with a brain tumour derived oncogene, EGFRvIII; an oncogenic form of epidermal growth factor receptor (EGFR) found in human malignant astrocytomas. The effect of EGFRvIII on neural stem cell self renewal, proliferation, differentiation and migration was studied. Results suggest that EGFRvII increases self renewal and proliferation of cells, and may alter neural stem cell differentiation and migration. The results establish an experimental model which explores early stages of brain tumorigenesis through expression and analysis of oncogenes in neural stem cells.

The Physical Object
Pagination52 leaves.
Number of Pages52
ID Numbers
Open LibraryOL19747846M
ISBN 100612915220

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This book is a collective work of international experts in the neural stem cell field. The book incorporates the characterization of embryonic and adult neural stem cells in both invertebrates and vertebrates. It highlights the history and the most advanced discoveries in neural stem cells, and summarizes the mechanisms of neural stem cell development. In particular, this book provides Cited by: 4. Human Neural Stem Cell Culture A stably immortalized human neural stem cell line, HB1.F3 (F3), was generated via transfection of fetal brain cells with a retroviral vector encoding the v-myc oncogene as reported previously F3 human neural stem cells were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM, Invitrogen.   Cell culture. Human neural stem/progenitor cells (hNSCs) were obtained from Millipore (Billerica, MA). The cells were derived from the ventral mesencephalon region of human fetal brain and immortalized by retroviral transduction with the v-myc by:   In this review, we discuss recent advancements in the direct reprogramming of fibroblasts into multipotent neural stem/progenitor cells (), and suggest criteria to successfully identify reprogrammed cells and perspectives for clinical ad: Download high-res image (KB) Download: Download full-size image Fig. 1.

Because neural stem cells have been described in a preceding chapter (Chapter 6) in this book, they will not be covered here to avoid redundancy. Table Cell lines covered in this chapter. The zebrafish brain combats Alzheimer’s disease by producing more neurons, which are derived from neural stem cells. By using single-cell sequencing technology, Cosacak et al. identify distinct stem cell populations that react differently to Alzheimer’s disease-like conditions in the adult zebrafish brain and develop tools to investigate their molecular programs.   Major developments in the neural stem cell (NSC) field in recent years provide new insights into the nature of the NSC niche. In this perspective, we integrate recent anatomical data on the organization of the two main neurogenic niches in the adult brain, the ventricular-subventricular zone (V-SVZ) and the subgranular zone (SGZ), with signaling pathways that control the behavior of NSCs.   A stringent in vivo Cre-dependent selection strategy was implemented to identify variants that transduce adult neural stem cells (NSCs) in the subventricular zone. A novel variant, SCH9, infected 60% of NSCs and mediated fold higher GFP expression and a fold greater transduction volume than AAV9.

  It is detailed that adult mouse neural stem cells (NSCs) express higher endogenous levels of Sox2 and c-Myc than embryonic stem cells, and that exogenous Oct4 together with either Klf4or c .   In the s, researchers showed that neural progenitor cells could be cultured as “neurospheres”—balls of cells that maintain self-replication and multipotency over protracted durations. This discovery led, in , to the first human neural stem cell transplant in a group of children with Batten disease, a rare neurodegenerative disorder.   By 2–10 days after transduction with Sox2, transformed cells had formed networks with colonies at the intersections of these networks (Figures 1B, S1A [Step 2], and S1B), many of which stained positive for Sox2 and Nestin (Figures 1C and S1C). The efficiency of generating Sox2 and Nestin double-positive colonies on gelatin-coated coverslips was % at day 8 postinfection and % at . Human neural stem cells. Recently in our UBC laboratory, stable immortalized cell lines of human NSC have been generated by introduction of myc oncogene. These immortalized NSC lines have advantageous characteristics for basic studies on neural development and cell replacement or gene therapy studies (6, 7): (i) NSC cell line can be expanded to large numbers in culture in short time .