Volume 8.37 | Sep 18

ESC & iPSC News 8.37 September 18, 2013
ESC & iPSC News
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Reprogramming In Vivo Produces Teratomas and Induced Pluripotent Stem Cells with Totipotency Features
The authors showed that transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs, implying that full reprogramming can occur in vivo. Analyses of the stomach, intestine, pancreas and kidney revealed groups of dedifferentiated cells that express the pluripotency marker NANOG, indicative of in situ reprogramming. By bone marrow transplantation, they demonstrated that hematopoietic cells can also be reprogrammed in vivo. [Nature] Abstract | Press Release
Take the 'if' out of 'diff': Reduce variability when differentiating to neural progenitors
PUBLICATIONS (Ranked by impact factor of the journal)
Safeguards for Cell Cooperation in Mouse Embryogenesis Shown by Genome-Wide Cheater Screen
Using a genome-wide screen in murine induced pluripotent stem cells, scientists identified a network of genes (centered on p53, topoisomerase 1, and olfactory receptors) whose down-regulation caused the cells to replace wild-type cells in vitro and in the mouse embryo-without perturbing normal development. [Science] Abstract | Press Release

Enhanced Survival of Transplanted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes by the Combination of Cell Sheets with the Pedicled Omental Flap Technique in a Porcine Heart
The cell-sheet method has been used to transplant many functional cells; however, potential ischemia might limit cell survival. The omentum, which is known to have rich vasculature, is expected to be a source of blood supply. Researchers hypothesized that transplantation of human induced pluripotent stem cell-derived cardiomyocyte (hiPS-CM) cell sheets combined with an omentum flap may deliver a large number of functional hiPS-CMs with enhanced blood supply. [Circulation] Abstract

Regulation of Pluripotency in Male Germline Stem Cells by Dmrt1
Researchers report that induction of global DNA hypomethylation in germline stem (GS) cells (cultured spermatogonial stem cells) induces pluripotent cell derivation. When DNA demethylation was triggered by Dnmt1 depletion, GS cells underwent apoptosis. [Genes Dev] Abstract

MicroRNA-Based Discovery of Barriers to Dedifferentiation of Fibroblasts to Pluripotent Stem Cells
Individual microRNAs (miRNAs) can target hundreds of mRNAs forming networks of presumably cooperating genes. To test this presumption, scientists functionally screened miRNAs and their targets in the context of dedifferentiation of mouse fibroblasts to induced pluripotent stem cells. [Nat Struct Mol Biol] Abstract

Driving Vascular Endothelial Cell Fate of Human Multipotent Isl1+ Heart Progenitors with VEGF Modified mRNA
Investigators identified a family of human cardiac endothelial intermediates located in outflow tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of Isl1 and CD144/vWF. By comparing angiocrine factors expressed by the human OFT-ECs and non-cardiac ECs, vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, and clonal assays documented its ability to drive endothelial specification of human embryonic stem cell-derived Isl1+ progenitors in a VEGF receptor-dependent manner. [Cell Res] Full Article

Spheroid Culture for Enhanced Differentiation of Human Embryonic Stem Cells to Hepatocyte-Like Cells
Researchers report cultivation of human embryonic stem cells as three-dimensional aggregates that enhances their differentiation to hepatocyte-like cells. [Stem Cell Dev] Abstract

Functional Analysis in Mouse Embryonic Stem Cells Reveals Wild-Type Activity for Three Msh6 Variants Found in Suspected Lynch Syndrome Patients
The authors previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the mutations in mismatch repair functions. They have adapted this method for the characterization of MSH6 missense mutations. [PLoS One] Full Article

CHIR99021 Promotes Self-Renewal of Mouse Embryonic Stem Cells by Modulation of Protein-Encoding Gene and Long Intergenic Non-Coding RNA Expression
Scientists identified CHIR99021 (CHIR)-regulated genes in mouse embryonic stem cells using microarray analysis. Their microarray data demonstrated that CHIR not only influenced the Wnt/β-catenin pathway by stabilizing β-catenin, but also modulated several other pluripotency-related signaling pathways such as TGF-β, Notch and MAPK signaling pathways. [Exp Cell Res] Abstract

Tracking Induced Pluripotent Stem Cell-Derived Neural Stem Cells in the Central Nervous System of Rats and Monkeys
Investigators attempted to track induced pluripotent stem cell-derived neural stem cells in the rodent and primate central nervous system and explore their therapeutic viability for stem cell replacement in traumatic brain injury rats and monkeys with spinal cord injury. [Cell Reprogram] Abstract

Slow Turning Lateral Vessel Bioreactor Improves Embryoid Body Formation and Cardiogenic Differentiation of Mouse Embryonic Stem Cells
Scientists describe a method of embryoid body (EB) formation in hydrodynamic conditions using a slow-turning lateral vessel bioreactor and the subsequent differentiation of EBs into cardiomyocytes. [Cell Reprogram] Abstract

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Calcium Signaling of Human Pluripotent Stem Cell-Derived Cardiomyocytes
Researchers review what are known about the immature Ca2+-handling properties of human pluripotent stem cell-cardiomyocytes, at the levels of global transients and sparks, and the underlying molecular basis in relation to the development of various in vitro approaches to drive their maturation. [J Physiol] Abstract

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NeoStem Awarded $147,765 NIH Grant for Treatment of Skin Wounds in Scleroderma Patients
NeoStem, Inc. announced that it has received an award under the Small Business Innovative Research Program of $147,765 for the “Development of Adult Pluripotent Very Small Embryonic Like Stem Cells to Treat Skin Wounds in Scleroderma” from the National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases. [Neostem, Inc.] Press Release

Weill Cornell Medical College Receives $100 Million Gift from Joan and Sanford I. Weill and the Weill Family Foundation to Launch New Capital Campaign
Weill Cornell Medical College announced that it has received a $100 million gift from longtime benefactors Joan and Sanford I. Weill and the Weill Family Foundation to launch the Medical College’s $300 million Driving Discoveries, Changing Lives campaign dedicated to using the most advanced scientific approaches to rapidly translate research breakthroughs into innovative treatments and therapies for patients. [Weill Cornell Medical College] Press Release

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Advisers Declare Italian Stem-Cell Therapy ‘Unscientific’
A scientific advisory committee in Italy gave a decided thumbs down to a controversial stem-cell treatment slated for a €3 million, government-sponsored clinical trial. The committee had been appointed by the health minister to evaluate the clinical protocol proposed by the Brescia-based Stamina Foundation, which developed the therapy. [The Italian Medicines Agency, Italy] Press Release

Sequester Cuts May Have Driven NIH Grant Success Rates Down to 14% in 2013
The automatic spending cuts and other reductions to the National Institutes of Health’s (NIH’s) budget this year have caused slightly less damage than expected, said NIH Director Francis Collins. Preliminary data show that about 50 more grants were funded than projected, he said at a forum sponsored by Research!America. [National Institutes of Health, United States] Press Release

U.K. Parliamentarians Urge Government to Reshape Push for Open-Access Publishing
British parliamentarians are urging the government of the United Kingdom to alter its plans for transitioning to open-access (OA) publishing of research results. In a report, a committee of the House of Commons says the government should encourage greater use of free institutional repositories, rather than OA journals that charge per-paper fees for publishing. [House of Commons, United Kingdom] Press Release
NEW Cell Symposia: Using Stem Cells to Model and Treat Human Disease
November 21-23, 2013
Los Angeles, United States

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NEW Postdoctoral Position – Heart Disease and Human ES/iPS Cells (University of Pittsburgh, School of Medicine)

Postdoctoral Position – Stem Cell and Neurodegenerative Diseases (University of Connecticut Health Center)

Postdoctoral Position – Leukemia Biology (Northwestern University)

Technician Position – Stem Cells and Epigenetics (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Self-Renewal of Pluripotent Stem Cells (Icahn School of Medicine at Mount Sinai)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

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