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 Realizing the potential of stem cells in understanding cancer biology Publication of the Month Customer Feature: S. Steven Potter, PhD NuGEN Receives Patent for Global Nucleic Acid Amplification Attending the 17th Research Council Meeting of Japan Society of Plastic and Reconstructive Surgery? Ovation® Systems Family of RNA Amplification and Labeling Products Customer Spotlight Send us a link and a brief overview of your papers and posters enabled by NuGEN Ovation® Systems, and we'll consider your submission for an upcoming issue. |
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Realizing the potential of stem cells in understanding cancer biology The field of stem cell research has been making significant contributions to our understanding of embryonic development and hematopoiesis while powering advances in cancer biology, and target discovery and drug development. Recent studies investigating the nature of cancer initiation and progression have emphasized the heterogeneous nature of pre-cancerous and cancerous tissues. One important, but often rare, cancerous cell type is known as cancer stem cells. Due to their rarity in typically heterogeneous solid tumor specimens, performing genomic and whole transcriptome gene expression studies have not been fruitful in identifying what makes these highly potent cancerous cells unique. In this month's featured publication (see below), Cho et al., were able to use isolated and cultured breast cancer stem cells to develop a mouse model of human breast cancer. The authors were able to identify a set of unique, differentially expressed transcripts specific to this stem cell population by amplification of very small amounts of RNA collected from these isolated cells and analyzed on microarrays. Further investigation determined that these transcripts are also differentially regulated between two clinical groups of human patients showing differential rates of cancer progression and survival. The study demonstrates the feasibility of creating model systems using cancer stem cells and offers a powerful tool for better understanding molecular pathways in normal and cancer stem cells alike, ultimately, providing insights into cancer biology.  The approach used in the study also demonstrates that identifying and purifying specific sub-populations of cells from highly heterogeneous tissue samples yields significant advantages in reducing ambiguity and generating valuable and biologically significant results. With NuGEN Ovation® Systems these very limited RNA samples and can be effectively amplified and generate powerful data that reveal specific signatures providing clues to the biological mechanisms study results.
Publication of the Month  Isolation and Molecular Characterization of Cancer Stem Cells in MMTV-Wnt-1 Murine Breast Tumors
Robert W. Cho, Xinhao Wang, Maximilian Diehn, Kerby Shedden, Grace Y. Chen, Gavin Sherlock, Austin Gurney, John Lewicki, Michael F. Clarke Stem Cells Vol. 26 No. 2 February 2008, pp. 364 -371; doi:10.1634/stemcells.2007-0440 Abstract In human breast cancers, a phenotypically distinct minority population of tumorigenic (TG) cancer cells (sometimes referred to as cancer stem cells) drives tumor growth when transplanted into immunodeficient mice. Our objective was to identify a mouse model of breast cancer stem cells that could have relevance to the study of human breast cancer. To do so, we used breast tumors of the mouse mammary tumor virus (MMTV)-Wnt-1 mice. MMTV-Wnt-1 breast tumors were harvested, dissociated into single-cell suspensions, and sorted by flow cytometry on Thy1, CD24, and CD45. Sorted cells were then injected into recipient background FVB/NJ female syngeneic mice. In six of seven tumors examined, Thy1+CD24+ cancer cells, which constituted approximately 1%-4% of tumor cells, were highly enriched for cells capable of regenerating new tumors compared with cells of the tumor that did not fit this profile ("not-Thy1+CD24+"). Resultant tumors had a phenotypic diversity similar to that of the original tumor and behaved in a similar manner when passaged. Microarray analysis comparing Thy1+CD24+ tumor cells to not-Thy1+CD24+ cells identified a list of differentially expressed genes. Orthologs of these differentially expressed genes predicted survival of human breast cancer patients from two different study groups. These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells. Other stem cell research publications enabled by NuGEN Ovation® Systems: HOXB4's road map to stem cell expansion Bernhard Schiedlmeier, Ana Cristina Santos, Ana Ribeiro, Natalia Moncaut, Dietrich Lesinski, Herbert Auer, Karl Kornacker, Wolfram Ostertag, Christopher Baum, Moises Mallo, and Hannes Klump. PNAS, October 23, 2007, vol. 104, no. 43, 16952-16957 Zscan4: a novel gene expressed exclusively in late 2-cell embryos and embryonic stem cells Geppino Falco, Sung-Lim Lee, Ilaria Stanghellini, Uwem C. Bassey, Toshio Hamatani and Minoru S. H. Ko Published online 2007 May 8. doi: 10.1016/j.ydbio.2007.05.003 Derivation of human embryonic stem cells from developing and arrested embryos Xin Zhang, Petra Stojkovic , Stefan Przyborski, Michael Cooke, Lyle Armstrong, Majlinda Lako, Miodrag Stojkovic. Stem Cells Express, published online September 2006; doi:10.1634/stemcells.2006-0377 The Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-dioxin Alters the Circadian Rhythms, Quiescence, and Expression of Clock Genes in Murine Hematopoietic Stem and Progenitor Cells Russell W. Garrett and Thomas A. Gasiewicz. Mol. Pharmacology, June 2006, 69 (6):2076-2083 Neurocytoma Is a Tumor of Adult Neuronal Progenitor Cells Fraser J. Sim,1* H. Michael Keyoung,2* James E. Goldman,3 Dong Kyu Kim,4 Hee-Won Jung,4 Neeta S. Roy,2 and Steven A. Goldman1,2. The Journal of Neuroscience, November 29, 2006 - 26(48):12544-12555 Customer Feature S. Steven Potter, PhD Professor of Pediatrics Division of Developmental Biology Cincinnati Children's Hospital Medical Center 
Dr. Potter is pictured here with his team. Photos are kindly provided by Cincinnati Children's Hospital Medical Center http://www.cincinnatichildrens.org/ "One of our projects is focused on better understanding the genetic program that drives kidney development. This work grew out of a collaboration with Mario Capecchi, Co-Chairman of the Department of Human Genetics, University of Utah School of Medicine, in which we showed that Hox genes play key roles with functional redundancies in kidney organogenesis. Kidney development is based on differential cell type specific expression of a vast number of genes. While multiple critical genes and pathways have been elucidated, a genome-wide analysis of gene expression within individual cellular and micro-anatomic structures has been lacking. Accomplishing this could provide significant new insights into fundamental developmental mechanisms such as mesenchymal-epithelial transition, inductive signaling, branching morphogenesis, and segmentation. We have been using laser-capture microdissection to isolate the intermediate components of nephron formation, including cap mesenchyme, renal vesicles, S-shaped bodies, early proximal tubules and loop of Henle, renal corpuscle, collecting ducts, and many others. Microarrays are then used to generate global, quantitative and sensitive expression profiles of these compartments. The results provide a comprehensive gene expression atlas of the developing kidney, which can then be used to define the changing gene expression program during nephrogenesis, to discover novel growth factor-receptor interactions, and to provide deeper insight into the genetic regulatory mechanisms of kidney development. This atlas also provides a baseline of normal development that can be used for a global analysis of gene expression perturbations that occur in mutants. We have used a similar strategy to study the kidney disease focal segmental glomerulosclerosis (FSGS), which is the most common acquired cause of kidney failure in children. This disease is poorly understood, refractory to treatment, and generally results in the gradual scarring of the glomeruli and loss of kidney function. Again, we used laser-capture microdissection coupled with microarrays to compare normal and diseased gene expression patterns to identify altered processes and functions associated with this disease. Our studies require a high level of sensitivity and reproducibility in working with small and often compromised LCM samples. We are using the NuGEN WT-Ovation™ Pico System to address these challenges." View a list of recent publications by Dr. Potter and his team. NuGEN Receives Patent for Global Nucleic Acid Amplification  NuGEN announced in July that the company has received US Patent No. 7,402,386, "Global amplification using random priming by a composite primer." The patent describes a global whole genome amplification methodology using composite DNA/RNA primers able to anneal to multiple sites within the template polynucleotide. The resulting amplified nucleic acid is suitable for use with a wide array of investigative approaches and applications. Nurith Kurn, NuGEN co-founder and chief scientific officer noted, "This new technology will further enable the use of valuable and precious biological samples to accelerate the understanding of disease pathologies, and target discovery and validation."
Global whole genome amplification is a new area of focus for NuGEN. The company plans to expand its family of products in 2009 to include new solutions and workflows with DNA amplification. Attending the 17th Research Council Meeting of Japan Society of Plastic and Reconstructive Surgery? Stop by the MediBic booth and learn about NuGEN Solutions.  The 17th Research Council Meeting of Japan Society of Plastic and Reconstructive Surgery
October 2-3, 2008, Tokyo, Japan Ovation® Systems Family of RNA Amplification and Labeling Products  The NuGEN Ovation® Systems family of RNA amplification and labeling products enables sensitive, robust gene expression profiling and novel signature discovery using a variety of challenging biological samples such as FFPE, whole blood, LCM, fine needle aspirates, tissue biopsies, sorted cell, and more. The flexible modular products let you chose your preferred analytical platform; Affymetrix 3' or Exon, Agilent, or Illumina microarrays, and qPCR.
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