ESC & iPSC News 13.47 November 28, 2018 | |
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TOP STORYCDK12 Regulates DNA Repair Genes by Suppressing Intronic Polyadenylation Scientists showed that CDK12 globally suppresses intronic polyadenylation events in mouse embryonic stem cells, enabling the production of full-length gene products. [Nature] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Predicting the Mutations Generated by Repair of Cas9-Induced Double-Strand Breaks Investigators systematically studied the influence of flanking DNA sequence on repair outcome by measuring the edits generated by >40,000 guide RNAs in synthetic constructs. They performed the experiments in a range of genetic backgrounds and using alternative CRISPR-Cas9 reagents. [Nat Biotechnol] Abstract Polycomb-associated DNA methylation valleys, hypomethylated domains encompassing developmental genes, became methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occured during differentiation of Dnmt3aW326R pluripotent cells in vitro, and was also evident in Dnmt3aW326R/+ dwarf mice. [Nat Genet] Abstract Scientists identified epigenetic features of mouse ESCs cultured using two small-molecule inhibitor (2i)/leukemia inhibitory factor (LIF) or serum/LIF by proteomic profiling of chromatin-associated complexes and histone modifications. Polycomb-repressive complex 2 (PRC2) and its product H3K27me3 were highly abundant in 2i/LIF ESCs, and H3K27me3 was distributed genome-wide in a CpG-dependent fashion. [Cell Stem Cell] Abstract | Graphical Abstract Generation of Human Antral and Fundic Gastric Organoids from Pluripotent Stem Cells The human stomach contains two primary domains: the corpus, which contains the fundic epithelium, and the antrum. Each of these domains has distinct cell types and functions, and therefore each presents with unique disease pathologies. Researchers detail two protocols to differentiate human PSCs into human gastric organoids that recapitulate both domains. [Nat Protoc] Abstract By altering the media in which injected morulae are cultured, investigators observed increased survival of cynomolgus monkey primed ESCs, induced PSCs, and somatic cell nuclear transfer-derived ESCs, thereby enabling chimeric contributions with 0.1%–4.5% chimerism into the embryonic and placental tissues, including germ cell progenitors in chimeric monkeys. [Cell Rep] Full Article | Graphical Abstract Dppa3 Is Critical for Lin28a-Regulated ES Cells Naïve-Primed State Conversion Scientists demonstrated that Dppa3 functions predominantly downstream of Lin28a during naïve-primed state conversion. Higher level of Lin28a prevented let-7 maturation and resulted in Dnmt3a/b upregulation, which in turn induced hypermethylation of the Dppa3 promoter. [J Mol Cell Biol] Abstract Partial Reprogramming Induces a Steady Decline in Epigenetic Age before Loss of Somatic Identity Researchers analyzed the dynamics of cellular age during human iPSC reprogramming and found that partial reprogramming leads to a reduction in the epigenetic age of cells. [Aging Cell] Full Article Transient inhibition of c‐Src during endodermal induction of human iPSCs reduced endodermal commitment and expression of endodermal markers including SOX17 and FOXA2 in a dose dependent manner. The transiently treated cells later developed into profibrogenic cholangiocyte‐like cells expressing both cholangiocyte markers such as CK7 and CK19 and fibrosis markers including collagen1 and SMA. [Stem Cells] Abstract Scientists suggested that the R1746Q mutation interferes with the function of centrosomal protein of 290 kDa (CEP290) to maintain the ciliary diffusion barrier and disrupts the integrity of the molecular composition in the primary cilium, which may contribute to alterations in neuroarchitecture. [Sci Rep] Full Article Subscribe to one of our other 19 science newsletters such as Cell Therapy News & Mesenchymal Cell News. | |
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REVIEWSThe authors cover the cutting edge in vascular smooth muscle cell modeling of elastin-associated vasculopathy, and aid in the development of human disease modeling and drug screening approaches to identify potential treatments. [Cell Mol Life Sci] Abstract Modeling Myeloid Malignancies with Patient-Derived iPSCs Recent studies of iPSC modeling of myeloid malignancies exploited the clonal heterogeneity of patient samples to derive genetically matched normal controls and recapitulate the clonal evolution of the disease. Comparisons of the malignant phenotypes and molecular signatures of primary leukemic cells, derived iPSCs and their hematopoietic progeny stress the importance of the cell-of-origin in oncogenesis and enable investigation of the interplay between cell identity and the cancer genome. [Exp Hematol] Abstract Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field. | |
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INDUSTRY NEWSOrgenesis Inc. announced that it has entered into a collaboration agreement with the New York Blood Center (NYBC). Under the agreement, NYBC will be responsible for establishing the infrastructure to collect, process, test, cryopreserve and biobank sampling materials, including liver biopsies. [Orgenesis Inc.] Press Release Asterias Biotherapeutics, Inc. announced enrollment and dosing of the fourth subject in the first-in-human Phase I clinical trial of VAC2 in the United Kingdom. VAC2 is an innovative immunotherapy product that contains mature dendritic cells derived from pluripotent stem cells. [Asterias Biotherapeutics, Inc.] Press Release | |
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POLICY NEWSRomania Cuts Research Budget for Second Time This Year The Romanian government has sliced off another €49 million from its research budget, as the ministry for research and innovation failed to put out funding calls to spend all of the €350 million it had allocated for 2018. [Science|Business] Editorial Some Research May Be Encouraging Ineffective Prescriptions, Says New Study A new paper published by McGill University researchers in JAMA Internal Medicine suggests that some clinical trials may promote the use of ineffective and costly treatments. That’s the opposite of what clinical trials are aimed at, namely preventing ineffective and costly treatments from being taken up by physicians and patients. [McGill University] Editorial Researcher Who Created CRISPR Twins Defends His Work but Leaves Many Questions Unanswered The researcher who set off a global firestorm when he announced the birth of the world’s first gene-edited babies defended his study at a meeting. He Jiankui of the Southern University of Science and Technology in nearby Shenzhen, China, said he was “proud” of the work, which he said could lead to disease prevention “for millions of children,” and provided some details about the unpublished research that many scientists and bioethicists—as well as a phalanx of journalists—were clamoring to hear. [ScienceInsider] Editorial
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EVENTSNEW EMBO-EMBL Symposia: Mechanical Forces in Development Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESScientist – Cell Culture Media and Cell Line Development (STEMCELL Technologies Inc.) Assistant/Associate Adjunct Professor – Cardiovascular Medicine (UC Davis) Postdoctoral Position – iPSC Models of Neurodegenerative Disease (Johns Hopkins School of Medicine) Research Associate – Clinical Grade Production of Blood Cells from PSCs (University of Cambridge) Postdoctoral Position – Stem Cells and Diabetes (A*STAR) Postdoctoral Fellows – iPSCs & Blood Development (University of Washington) Postdoctoral Research Scientist – Precision Medicine (Columbia University) Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University) 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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