ESC & iPSC News 12.17 May 3, 2017 | |
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TOP STORYResearchers at Indiana University (IU) School of Medicine have successfully developed a method to grow inner ear tissue from human stem cells — a finding that could lead to new platforms to model disease and new therapies for the treatment of hearing and balance disorders. [Press release from the Indiana University (IU) School of Medicine discussing online prepublication in Nature Biotechnology] Press Release | Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Scientists present multiple lines of evidence that a eutherian-specific multicopy retrogene, DUX4, encodes a transcription factor that activates hundreds of endogenous genes and retroviral elements that define the cleavage-specific transcriptional programs in humans and mice. [Nat Genet] Abstract Naive pluripotent stem cells utilize both glycolysis and oxidative phosphorylation to satisfy their metabolic demands. The authors showed that when transduced with Oct4, Sox2, and Klf4 into murine fibroblasts, Zic3 and Esrrb synergistically enhanced the reprogramming efficiency by regulating cellular metabolic pathways. These two transcription factors cooperatively activate glycolytic metabolism independently of hypoxia inducible factors. [Cell Metab] Abstract | Graphical Abstract Researchers engineered and developmentally differentiated NK2 homeobox 1–expressing (NKX2)-1GFP reporter pluripotent stem cells in vitro to generate and isolate human primordial lung progenitors that express NKX2-1 but are initially devoid of differentiated lung lineage markers. In the absence of mesenchymal coculture support, this NKX2-1+ population was able to generate epithelial-only spheroids in defined 3D cultures. Alternatively, when recombined with fetal mouse lung mesenchyme, the cells recapitulated epithelial-mesenchymal developing lung interactions. [J Clin Invest] Full Article | Press Release FLI1 Level during Megakaryopoiesis Affects Thrombopoiesis and Platelet Biology Scientists studied induced-pluripotent stem cell (iPSC)-derived megakaryocytes (iMegs) to better understand clinical disorders, beginning with iPSCs generated from a Paris-Trousseau syndrome (PTSx) patient and iPSCs from a control line with a targeted heterozygous friend leukemia virus integration 1 (FLI1) knockout (FLI1+/-). PTSx and FLI1+/- iMegs replicated many of the described megakaryocyte/platelet features including a decrease in iMeg yield and fewer platelets released per iMeg. [Blood] Abstract Researchers report that in vitro differentiation of human embryonic stem cells (hESCs) to hepatic lineage undergoes a sequential epithelial to mesenchymal transition (EMT)-MET with an obligatory intermediate mesenchymal phase. They identified SNAI1 as the key EMT transcriptional factor required for the specification of definitive endoderm (DE). Genetic ablation of SNAI1 in hESCs did not affect the maintenance of pluripotency or neural differentiation, but completely disrupted the formation of DE. [Nat Commun] Full Article Disrupted Neuronal Maturation in Angelman Syndrome-Derived Induced Pluripotent Stem Cells The authors explored the underlying pathophysiology using induced pluripotent stem cell-derived neurons from Angelman syndrome (AS) patients and unaffected controls. AS-derived neurons showed impaired maturation of resting membrane potential and action potential firing, decreased synaptic activity and reduced synaptic plasticity. These patient-specific differences were mimicked by knocking out UBE3A using CRISPR/Cas9 or by knocking down UBE3A using antisense oligonucleotides. [Nat Commun] Full Article | Press Release Large-Scale Analysis of Loss of Imprinting in Human Pluripotent Stem Cells Researchers charted the landscape of loss of imprinting (LOI) in human pluripotent stem cells (hPSCs) by applying a large-scale analysis of allele-specific RNA-seq data from more than 270 hPSC samples. They showed that reprogrammed hPSCs acquire higher levels of LOI compared with embryonic stem cells and that LOI can pre-exist in their somatic cells of origin. [Cell Rep] Full Article | Graphical Abstract Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations Investigators showed that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents in midbrain neurons differentiated from induced pluripotent stem cells of Parkinson’s disease (PD) patients with parkin mutations, but not normal subjects. Overexpression of wild-type parkin, but not its PD-causing mutant, abolished the oscillatory activities in patient neurons. [Cell Rep] Full Article | Press Release | Graphical Abstract Genome Engineering of Stem Cells for Autonomously Regulated, Closed-Loop Delivery of Biologic Drugs Using the CRISPR/Cas9 genome-engineering system, the authors created stem cells that antagonize interleukin-1- or tumor necrosis factor α-mediated inflammation in an autoregulated, feedback-controlled manner. Their results showed that genome engineering can be used successfully to rewire endogenous cell circuits to allow for prescribed input/output relationships between inflammatory mediators and their antagonists, providing a foundation for cell-based drug delivery or cell-based vaccines via a rapidly responsive, autoregulated system. [Stem Cell Reports] Full Article Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming Scientists report that NANOG phosphorylation is beneficial, although nonessential, for embryonic stem cell self-renewal, and that loss of phosphorylation enhances NANOG activity in reprogramming. Mutation of serine 65 in NANOG to alanine alone had the most significant impact on increasing NANOG reprogramming capacity. [Stem Cell Reports] Full Article | Graphical Abstract STRIP2 Is Indispensable for the Onset of Embryonic Stem Cell Differentiation The role of striatin interacting protein 2 (Strip2) in differentiation of embryonic stem cells (ESCs) is still under debate. Researchers showed that Strip2 is distributed in the perinucleus or nuclei of wild-type undifferentiated ESCs, but is localized in high-density nuclear bodies in differentiated cells. [Mol Ther Methods Clin Dev] Full Article | |
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REVIEWSProtein Kinases in Pluripotency – Beyond the Usual Suspects The authors review recent progress in understanding the overarching role of phosphorylation in mediating communication from the cellular environment, metabolism and cell cycle to the core pluripotency machinery. [J Mol Biol] Full Article | Graphical Abstract Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field. | |
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SCIENCE NEWSPresentation on Asterias’ AST-OPC1 for Spinal Cord Injury Asterias Biotherapeutics, Inc. announced that data from its AST-OPC1 clinical program for severe cervical spinal cord injury will be presented. Data will be presented from the SCiStar study demonstrating the potential of AST-OPC1 to help patients with complete paralysis regain increased arm, hand and finger function, and thus greater ability to live independently. [Press release from Asterias Biotherapeutics, Inc. discussing research to be presented at the Presidential Symposium at the American Society of Gene and Cell Therapy (ASGCT) 20th Annual Meeting, Washington, D.C.] Press Release | Abstract | |
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INDUSTRY NEWSCIRM Announces Leadership Transition The California Institute for Regenerative Medicine (CIRM) announced that its President and Chief Executive Officer, C. Randal Mills, Ph.D., will be leaving to become the next President and CEO of the National Marrow Donor Program®/Be The Match®. Maria Millan, M.D., will succeed Dr. Mills as interim President and CEO of CIRM pending further action by the agency’s Presidential Search Subcommittee and full board. [California Institute for Regenerative Medicine] Press Release Asterias Biotherapeutics, Inc. announced that following a regularly scheduled interim review of safety data from its SCiStar Phase I/IIa clinical trial of AST-OPC1 for acute spinal cord injury, the study’s Data Monitoring Committee recommended continuation of enrollment for the 10 million cell and 20 million cell dose cohorts in the study, as planned. [Asterias Biotherapeutics, Inc.] Press Release DefiniGEN Licenses Cholangiocyte Stem Cell Technology from Cambridge Enterprise DefiniGEN announced that it has strengthened its IP portfolio with a license for cutting-edge cholangiocyte liver technology from Cambridge Enterprise. The technology will be used by DefiniGEN to develop optimized liver cell products and services for various applications, such as disease modeling, drug screening and therapeutic target validation. [DefiniGEN Ltd] Press Release | |
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POLICY NEWSNIH to Limit the Amount of Grant Money a Scientist Can Receive For the first time, the US National Institutes of Health (NIH) will restrict the amount of funding that an individual scientist can hold at any one time, based on a new point system. The move is part of an ongoing effort to make obtaining grants easier for early and mid-career scientists, who face much tougher odds than their more-experienced colleagues. [Nature News] Editorial Researchers Frustrated by Italian Misconduct Probe More than five years ago, Italian police began investigating allegations of research misconduct in papers by Alfredo Fusco, a prominent cancer scientist in Naples. Researchers frustrated by the case’s slow progress have told Nature that there is strong evidence that dozens of papers may contain manipulated data — and that a commercial photography studio was called in to cut and paste images. They say they are speaking out about the magnitude of the allegations because of their increasing impatience with the slow pace of investigations by police and by academic authorities. [Nature News] Editorial
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EVENTSNEW Mammalian Genetics and Genomics: From Molecular Mechanisms to Translational Applications Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Research Scientist – Cardiovascular (Columbia University Medical Center) Research Associate – Research and Development (STEMCELL Technologies, Inc.) Postdoctoral Position – Cellular Modeling of Diabetes (University of California, San Diego) Postdoctoral Position – Epigenetics of Pluripotent Stem Cells (Albert Einstein College of Medicine) Research Scientist – Stem Cell Biology (ArunA Biomedical, Inc.) Postdoctoral Fellow – Epigenetic Mechanisms (European Molecular Biology Laboratory) Postdoctoral Fellow – Stem Cells and Epigenetics (University of Michigan) Independent Group Leaders – Regenerative Medicine (Center for Regenerative Medicine) Group Leader – Induced Pluripotent Stem Cells and Brain Malignancies (German Cancer Research Center) Postdoctoral Research Associate – Developmental Neuroscience (University of Nebraska Medical Center) Postdoctoral Fellow – Multiple Areas (University of Oklahoma) Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center) Postdoctoral Fellow – Pluripotent Stem Cell Technology (University of California, Davis) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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