ESC & iPSC News 11.47 November 30, 2016 | |
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TOP STORYTissue Damage and Senescence Provide Critical Signals for Cellular Reprogramming In Vivo The process of OCT4, SOX2, KLF4, and cMYC reprogramming is inefficient both in vitro and in vivo. A number of cell-intrinsic barriers have been identified in vitro, most of which are activated by cellular damage and are particularly prominent in aged cells. Mechanistically, these cell-intrinsic barriers for reprogramming are primarily mediated by the tumor suppressors p53, p16INK4a, and ARF. Scientists investigated the effect of these tumor suppressors, cellular damage, and aging on in vivo reprogramming. [Science] Abstract | Press Release | Graphical Abstract | Video | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors employed a CRISPR/Cas9-mediated deletion approach to study the function of several enhancer clusters and isolated enhancers in mouse embryonic stem cells. [Genome Res] Abstract Investigators showed that human pluripotent stem cells exhibit increased assembly of the chaperonin TRiC/CCT complex, a mechanism induced by high levels of specific CCT subunits. [Nat Commun] Full Article | Press Release The authors report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs). Loss of USP21 results in Nanog degradation, mESCs differentiation and reduces somatic cell reprogramming efficiency. [Nat Commun] Full Article Researchers developed single-step optimized inducible gene knockdown or knockout (sOPTiKD or sOPTiKO) platforms. These are based on genetic engineering of human genomic safe harbors combined with an improved tetracycline-inducible system and CRISPR/Cas9 technology. They exemplify the efficacy of these methods in human pluripotent stem cells (hPSCs), and showed that generation of sOPTiKD/KO hPSCs is simple, rapid and allows tightly controlled individual or multiplexed gene knockdown or knockout in hPSCs and in a wide variety of differentiated cells. [Development] Full Article Investigators report on the effects of a single-copy deletion of the chr17p13.1 region, a sporadic mutation that spontaneously arose independently in several subclones of a human embryonic stem cell culture. Compared to cells with two normal copies of chr17p13.1 (“wild-type”), the cells with a single-copy deletion of this region (“mutant”) displayed a selective advantage when exposed to stressful conditions, and retained a higher percentage of cells expressing the pluripotency marker POU5F1/OCT4 after two weeks of in vitro differentiation. [Stem Cells] Abstract Researchers identified Geminin-associated chromatin locations in embryonic stem cells and Geminin- and Zic1-associated locations during neural fate acquisition at a genome-wide level. [Sci Rep] Full Article The Mevalonate Pathway Regulates Primitive Streak Formation via Protein Farnesylation The primitive streak in peri-implantation embryos forms the mesoderm and endoderm and controls cell differentiation. The metabolic cues regulating primitive streak formation remain largely unknown. Scientists utilised a mouse embryonic stem cell differentiation system and a library of well-characterised drugs to identify these metabolic factors. [Sci Rep] Full Article Researchers demonstrated a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. [Mol Ther Nucleic Acids] Full Article CRISPR/Cas9-AAV Mediated Knock-in at NRL Locus in Human Embryonic Stem Cells Investigators demonstrate that using clustered interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-adeno-associated virus (AAV), they could successfully knock-in a DsRed reporter gene at the basic motifleucine zipper transcription factor (NRL) locus in human embryonic stem cells. [Mol Ther Nucleic Acids] Full Article Elimination of Proliferating Cells from CNS Grafts Using a Ki67 Promoter-Driven Thymidine Kinase Pluripotent stem cell (PSC)-based cell therapy is an attractive concept for neurodegenerative diseases, but can lead to tumor formation. This is particularly relevant as proliferating neural precursors rather than postmitotic mature neurons need to be transplanted. Thus, safety mechanisms to eliminate proliferating cells are needed. The authors propose a suicide gene approach, based on cell cycle-dependent promoter Ki67-driven expression of herpes simplex virus thymidine kinase. They generated a PSC line expressing this construct and induced neural differentiation. [Mol Ther Methods Clin Dev] Full Article | |
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REVIEWSLinking Telomere Regulation to Stem Cell Pluripotency The author discusses the link between telomere elongation and homeostasis to the acquisition and maintenance of stem cell pluripotency, and their regulatory mechanisms by epigenetic modifications. [Trends Genet] Abstract Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field. | |
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SCIENCE NEWSPositive Early Data From BioTime’s Renevia Pivotal Trial BioTime, Inc. announced details of positive data from its Renevia® pivotal trial. The presentation was based on data from the “run-in,” testing sample subjects to the European pivotal trial. The Renevia administration procedure was found to be reproducible, and the pivotal trial is now into its controlled phase. Encouraging signs of Renevia being able to promote new tissue generation were seen with the run-in practice patients. If the pivotal trial is successful, the company plans to file the data as the basis for the issuance of CE marking for European use. [Press release from BioTime, Inc. discussing research presented at the 14th annual International Federation for Adipose Therapeutics and Science meeting (IFATS) , San Diego] Press Release | |
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INDUSTRY NEWSEvotec and Merck Enter into Agreements to Collaborate on Target Discovery Technologies Evotec AG announced the signing of a set of collaboration agreements with the life science business of Merck, which will combine Merck’s portfolio of genome editing technologies with Evotec’s versatile screening platforms and disease expertise. Evotec will leverage Merck’s comprehensive collection of genetic reagents such as viral CRISPR and shRNA libraries to enable new target discovery programmes using its capabilities for phenotypic screening in primary and induced pluripotent stem cells, as well as its in vivo disease models. [Evotec AG] Press Release Biological Industries Announces FDA Drug Master File Acceptance for NutriStem® hPSC XF Medium Biological Industries announced that the United States Food and Drug Administration (FDA) has accepted the submission for its Drug Master File for the company’s NutriStem® hPSC XF Medium, a commercially defined, xeno-free, serum-free media, which is designed to support the growth of human embryonic stem cells and induced pluripotent stem cells. [Biological Industries] Press Release Announcing the Allen Cell Collection The Allen Institute for Cell Science has released the Allen Cell Collection: the first publicly available collection of gene edited, fluorescently tagged human induced pluripotent stem cells that target key cellular structures with unprecedented clarity. Distributed through the Coriell Institute for Medical Research, these powerful tools are a crucial first step toward visualizing the dynamic organization of cells to better understand what makes human cells healthy and what goes wrong in disease. [Allen Institute] Press Release | Video ORIG3N announced that it has achieved a significant milestone in cell therapy and regenerative medicine: It has identified Human Leukocyte Antigen compatible matches within its LifeCapsule bank for 90 percent of the U.S. population. For the first time in human history, a complete set of matched samples has been identified and can be industrially produced. Utilizing induced pluripotent stem cell technology, any tissue can be generated from these cells, and they can be an exact allogeneic match to the individuals requiring them. [ORIG3N, Inc.] Press Release | |
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POLICY NEWSNew U.S. Research Policy Board Would Aim to Slash Regulatory Paperwork Easing the regulatory burden on U.S. academic research certainly isn’t as sexy as curing cancer or understanding how the brain works. But creating an advisory body focused on eliminating government red tape—a tiny provision in a 996-page bill to accelerate medical research that could become law next month—is no less important to maintaining the health of the research community than is the infusion of billions of dollars, higher education lobbyists say. [ScienceInsider] Editorial UK Moves Closer to Allowing ‘Three-Parent’ Babies The United Kingdom may soon become the first country to explicitly permit the birth of children from embryos modified to contain three people’s DNA. At the same time, new research backs up concerns that such a treatment — which aims to erase diseases transmitted by the DNA found in cellular structures called mitochondria — may not always be 100% effective. [Nature News] Editorial Trump’s Pick for US Health Secretary Has Pushed to Cut Science Spending Republican congressman Tom Price of Georgia is US President-elect Donald Trump’s pick to head the US Department of Health and Human Services. If he is confirmed by the Senate, Price would oversee the National Institutes of Health, the Centers for Disease Control and Prevention and the Food and Drug Administration. [Nature News] Editorial Tracking the Trump Transition, Agency by Agency As US president-elect Donald Trump begins to sketch out the priorities of his administration, Nature tracks the key issues and likely leaders of vital science and research agencies. [Nature News] Editorial
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EVENTSNEW Cold Spring Harbor Stem Cell Biology Meeting Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Researcher – ESC/iPSC Differentiation (Helmholtz Association) NEW Faculty Researcher – Stem Cell Biology (Stanford University) Postdoctoral Researcher – Developmental Biology (RIKEN) Research Assistant – Human Germ Cell Biology (University of Cambridge) Senior Scientist – Regenerative Medicine (Astellas) NYSCF Investigator – Stem Cell And Neuroscience (New York Stem Cell Foundation) Postdoctoral Fellow – Neural Stem/Progenitor Cells (University of California – San Francisco) 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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Home ESC & iPSC News Volume 11.47 | Nov 30 2016