Volume 8.09 | Mar 6

ESC & iPSC News 8.09 March 6, 2013
ESC & iPSC News
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Reprogramming Adult Cells to Stem Cells Works Better with One Gene Turned Off
The removal of a genetic roadblock could improve the efficiency of converting adult cells into stem cells by 10 to 30 times. Researchers identified a protein encoded by the gene Jmjd3 as a roadblock in the stem cell conversion process. They found knockdown or deletion of Jmjd3 in young mouse fibroblasts was enough to greatly enhance reprogramming efficiency. [Press release from The Methodist Hospital System discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

Gain Hands-On Training. New Course: Differentiation of hPSCs to Neural Progenitor Cells
PUBLICATIONS (Ranked by impact factor of the journal)

Interaction Domains of Sos1/Grb2 Are Finely Tuned for Cooperative Control of Embryonic Stem Cell Fate
The Ras guanine nucleotide exchange factor Sos1 and its adaptor Grb2 are multidomain proteins that couple fibroblast growth factor signaling to activation of the Ras-Erk pathway during mammalian development and drive embryonic stem cells toward the primitive endoderm (PrE) lineage. Researchers showed that the ability of Sos1/Grb2 to appropriately regulate pluripotency and differentiation factors and to initiate PrE development requires collective binding of multiple Sos1/Grb2 domains to their protein and phospholipid ligands. [Cell] Abstract | Graphical Abstract

Interplay of LRRK2 with Chaperone-Mediated Autophagy
Investigators found leucine-rich repeat kinase 2 (LRRK2) to be degraded in lysosomes by chaperone-mediated autophagy (CMA), whereas the most common pathogenic mutant form of LRRK2, G2019S, was poorly degraded by this pathway. Cells responded to LRRK2-mediated CMA compromise by increasing levels of the CMA lysosomal receptor, as seen in neuronal cultures and brains of LRRK2 transgenic mice, induced pluripotent stem cell-derived dopaminergic neurons and brains of Parkinson’s disease patients with LRRK2 mutations. [Nat Neurosci] Abstract | Press Release

Arf Tumor Suppressor and MicroRNA-205 Regulate Cell Adhesion and Formation of Extraembryonic Endoderm from Pluripotent Stem Cells
Although the p19Arf protein is not detected in most tissues of fetal or young adult mice, it is physiologically expressed in the fetal yolk sac, a tissue derived from the extraembryonic endoderm (ExEn). Expression of the mouse p19Arf protein marks late stages of ExEn differentiation in cultured embryoid bodies (EBs) derived from either embryonic stem cells or induced pluripotent stem cells. Arf inactivation delays differentiation of the ExEn lineage within EBs, but not the formation of other germ cell lineages from pluripotent progenitors. [Proc Natl Acad Sci USA] Abstract | Full Article

An Ex Vivo Gene Therapy Approach to Treat Muscular Dystrophy Using Inducible Pluripotent Stem Cells
Researchers showed the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem cells generated from fibroblasts of mice lacking both dystrophin and utrophin. They corrected the phenotype of dystrophic induced pluripotent stem cells using a Sleeping Beauty transposon system carrying the micro-utrophin gene, differentiated these cells into skeletal muscle progenitors and transplanted them back into dystrophic mice. [Nat Commun] Abstract | Press Release

MacroH2A Histone Variants Act as a Barrier Upon Reprogramming towards Pluripotency
Using fibroblasts derived from macroH2A double knockout mice, researchers showed that these histone variants act cooperatively as a barrier to induced pluripotency. Through manipulation of macroH2A isoforms, they further demonstrated that macroH2A2 is the predominant barrier to reprogramming. [Nat Commun] Abstract

Activation of PDK-1 Maintains Mouse Embryonic Stem Cell Self-Renewal in a PKB-Dependent Manner
By using a modified Flp recombinase system, researchers expressed activated alleles of 3-phosphoinositide-dependent protein kinase-1 (PDK-1) and protein kinase B (PKB) to create stable, isogenic embryonic stem cell lines to further study the role of the phosphatidylinositol 3′ kinase signaling pathway in stem cell fate determination. [Oncogene] Full Article

Derivation of a Germline Competent Transgenic Fischer 344 Embryonic Stem Cell Line
Fischer344 (F344) males carrying an enhanced green fluorescence protein (EGFP) transgene were used as the founder animals for the derivation of embryonic stem (ES) cell lines. One male ES cell line, F344-Tg.EC4011, was further evaluated for germline competence by injection into Dark Agouti X Sprague Dawley (SD) blastocysts. Resulting chimeric animals were bred with wild-type SD mates and germline transmissibility of the ES cell line was confirmed by identification of pups carrying the ES cell line-derived EGFP transgene. [PLoS One] Full Article

Lamin A/C Haploinsufficiency Modulates the Differentiation Potential of Mouse Embryonic Stem Cells
Researchers investigated the differentiation potential of mouse embryonic stem cells containing reduced levels of lamin A/C by detailed lineage analysis of embryoid bodies derived from these cells by in vitro culture. [PLoS One] Full Article

New TeSR™-E8™ is Here For Feeder-Free Culture of Human ES Cells and iPS Cells

Stem Cells: A New Paradigm for Disease Modeling and Developing Therapies for Age-Related Macular Degeneration
Human embryonic stem cells and induced pluripotent stem cells have been used in cell culture assays and in vivo animal models. Recently a clinical trial was approved by FDA to investigate the safety and efficacy of the human embryonic stem cell-derived retinal pigment epithelium transplantation in sub-retinal space of patients with dry age-related macular degeneration (AMD). These studies suggest that stem cell research may provide both insight regarding disease development and progression, as well as direction for therapeutic innovation for the millions of patients afflicted with AMD. [J Transl Med] Abstract | Full Article

Stem Cells for Drug Developers | March 19-21, 2013 | Boston

BioTime and Subsidiary LifeMap Sciences Announce Data Mining Collaboration
BioTime, Inc. and its bioinformatics subsidiary LifeMap Sciences, Inc. announced that they have entered into a definitive collaboration agreement to utilize LifeMap’s computer-based tools to extract information relating to novel potential commercial products from nearly 100 million proprietary gene expression data points generated and owned by BioTime. The assembled data relate to BioTime’s proprietary PureStem™ progenitor cell lines derived from human embryonic stem cells. [BioTime, Inc.] Press Release

McGovern Institute Hands Out Neuroscience Award
The McGovern Institute for Brain Research at Massachusetts Institute of Technology has announced that Thomas Jessell of Columbia University is the winner of the 2013 Edward M. Scolnick Prize in Neuroscience. Jessell’s work has revealed the molecular mechanisms responsible for establishing the spatial organization of the spinal cord. He has identified diffusible signaling molecules that act during early development to provide “positional information” to embryonic cells, instructing them to differentiate in ways that are appropriate for their specific locations within the cord. [Massachusetts Institute of Technology]
Press Release


Lackluster Budget Leaves Indian Scientists Little to Cheer
Indian scientists face major belt-tightening in the coming year. The Indian government sent to Parliament for approval a $12 billion budget for science and technology (S&T) in 2013, ending several years of substantial increases for S&T. The flat budget, reflecting the government’s desire to reduce an almost $85 billion deficit, will equate to spending reductions with inflation running at about 5%. [Government of India, India]
Press Release

New Science Body to Advise European Commission President
The European Commission has set up a science advisory body that will report directly to its president, José Manuel Barroso. The Science and Technology Advisory Council will identify areas where research and innovation can contribute to Europe’s growth-with a particular focus on benefits and risks of science and technology advances and how to communicate these. [The European Commission, European Union]
Press Release

€300 Million Investment in Seven World-Class Research Centers – Minister Bruton, Minister Sherlock
Richard Bruton TD, Minister for Jobs, Enterprise and Innovation and Sean Sherlock, TD, Minister for Research and Innovation announced a landmark investment by the Government in scientific research. €200 million of Irish exchequer funding will be invested in seven world class research centers of scale. The new funding will be delivered through Science Foundation Ireland’s Research Centers Program coupled with over €100 million in cash and in-kind contributions from industry partners, making it the largest ever combined state/industry co-funding announcement of its kind in the research field in Ireland. [Science Foundation Ireland, Ireland] Press Release

FRC’s Dr. David Prentice Congratulates Kansas Senate for Passing Ethical Stem Cell Therapy Bill
Family Research Council (FRC) Senior Fellow Dr. David Prentice congratulated the Kansas state senate for passing S.B. 199, a bill that would establish the Midwest Stem Cell Therapy Center, a regional hub to advance and deliver adult and cord blood stem cell therapies to patients and serving as a resource for adult and cord blood stem cells for therapies. The Center would also inform professionals and the public about such therapies. [Family Research Council, United States] Press Release


NEW Experimental Biology (EB) 2013
April 20-24, 2013
Boston, United States

NEW The 2013 Stem Cell Event Trilogy
June 4-6, 2013
London, United Kingdom

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Senior Postdoctoral Position (Vrije Universiteit Brussel, Department of Biology)

Postdoctoral Position – iPS Cells in CNS Diseases (AbbVie Deutschland GmbH & Co. KG)

Postdoctoral Fellow – Cardiovascular Stem Cell (Yale University, School of Medicine)

Postdoctoral Position (University of Rochester Medical Center)

Postdoctoral Position – Stem Cell Research (University of Washington)

Lecturer or Reader – Associate Professor (University of Reading)

Postdoctoral Fellow (Johns Hopkins School of Medicine)

Postdoctoral Fellow – Pluripotent Stem Cells (Faculty of Medicine, University of Ottawa)

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