ESC & iPSC News 14.15 April 24, 2019 | |
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TOP STORYMammalian ISWI and SWI/SNF Selectively Mediate Binding of Distinct Transcription Factors Researchers generated viable embryonic stem cells that lacked SNF2H, the ATPase of ISWI complexes, enabling study of SNF2H cellular function, and contrasted it to BRG1, the ATPase of SWI/SNF. Loss of SNF2H decreased nucleosomal phasing and increased linker lengths, providing in vivo evidence for an ISWI function in ruling nucleosomal spacing in mammals. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)Intrinsic Apoptosis Shapes the Tumor Spectrum Linked to Inactivation of the Deubiquitinase BAP1 Investigators showed that BAP1 inactivation caused apoptosis in mouse embryonic stem cells, fibroblasts, liver, and pancreatic tissue but not in melanocytes and mesothelial cells. Ubiquitin ligase RNF2, which silenced genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing expression of the prosurvival genes Bcl2 and Mcl1. [Science] Abstract Unbiased Detection of CRISPR Off-Targets In Vivo Using DISCOVER-Seq The authors developed discovery of in situ Cas off-targets and verification by sequencing (DISCOVER-Seq), a universally applicable approach for unbiased off-target identification that leveraged the recruitment of DNA repair factors in cells and organisms. Tracking the precise recruitment of MRE11 uncovered the molecular nature of Cas activity in cells with single-base resolution. [Science] Abstract Using a dual-lineage differentiation system, scientists reported long-range topologically associating domains (TAD)–TAD interactions that formed constitutive and variable TAD cliques. A differentiation-coupled relationship between TAD cliques and lamina-associated domains suggested that TAD cliques stabilized heterochromatin at the nuclear periphery. [Nat Genet] Abstract Investigators showed that Krüppel-associated box-containing zinc finger proteins controlled the timely and pleiotropic activation of transposable element (TE)-derived transcriptional cis regulators during early embryogenesis. Evolutionarily recent SVA, HERVK, and HERVH TE subgroups contributed significantly to chromatin opening during human embryonic genome activation and are KLF-stimulated enhancers in naive human ESCs. [Cell Stem Cell] Full Article | Graphical Abstract Researchers demonstrated that episomal reprogramming of myelodysplastic syndromes patient samples generated iPSCs from single premalignant cells with a partial complement of mutations, directly informing the temporal order of mutations in the individual patient. Reprogramming preferentially captured early subclones with fewer mutations, which were rare among single patient cells. [Blood] Abstract TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network Scientists conducted a CRISPR-Cas9-mediated loss-of-function genetic screen that identified two epigenetic regulators, TAF5L and TAF6L, components or co-activators of the GNAT-HAT complexes for the mouse ESC state. Detailed molecular studies demonstrated that TAF5L/TAF6L transcriptionally activated c-Myc and Oct4 and their corresponding MYC and CORE regulatory networks. [Mol Cell] Abstract | Graphical Abstract MicroRNA-Deficient Mouse Embryonic Stem Cells Acquire a Functional Interferon Response The authors showed that, in the absence of miRNAs, ESCs acquired an active type I Interferon (IFN) response. Proteomic analysis identified MAVS, a central component of the IFN pathway, to be actively silenced by miRNAs and responsible for suppressing IFN expression in ESCs. [Elife] Abstract Scientists tested a set of long terminal repeat transposable element (TE) families for roles as enhancers in mouse embryonic and trophoblast stem cells. Epigenomic and transcriptomic data suggested that a large number of TEs helped to establish tissue-specific gene expression programmes. Genetic editing of individual TEs confirmed a subset of these regulatory relationships. [Elife] Abstract Investigators found that undifferentiated human PSCs (hPSCs) present in the cultures of neural stem/precursor cells completely disappeared within several days when cultured under neural differentiation culture conditions. Intriguingly, the disappearance of undifferentiated cells was not due to cell death, but was instead mediated by neural conversion of hPSCs. [Mol Ther] Abstract | Graphical Abstract Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells Researchers employed CRISPR/Cas9 to tag endogenous Yes-associated protein (YAP) in hPSCs and used this fusion protein to identify YAP’s interaction partners. This engineered cell line revealed that neural differentiation promoted a change in YAP interactors, including a dramatic increase in angiomotin interaction with YAP. [Stem Cell Reports] Full Article | Graphical Abstract Using proteomic approaches, investigators utilized human iPSCs for modeling intrablastocyst infection with influenza virus to not only investigate the vulnerability and responses of pluripotent stem cells to this virus but also to determine the possible impacts of influenza on pluripotency and signaling pathways controlling differentiation and embryogenesis. [Cell Death Dis] Full Article Scientists described a universal genome correction strategy to restore coagulation factor VIII (FVIII) expression in iPSCs derived from a patient with hemophilia A by human elongation factor 1 alpha (EF1α)-mediated normal FVIII gene expression in the FVIII locus of the patient. They used the CRISPR/Cas9-mediated homology-directed repair system to insert the B-domain deleted from the FVIII gene with the human EF1α promoter. [Exp Mol Med] Full Article Subscribe to one of our other 19 science newsletters such as Cell Therapy News & Mesenchymal Cell News. | |
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REVIEWSFrom Embryonic Stem Cells to Induced Pluripotent Stem Cells – Ready for Clinical Therapy? The authors review the generation and uses of ESCs compared to iPSCs, and discuss their advantages and limitations. They also evaluate the feasibility of clinical therapies and the future prospects for induced pluripotent cell-based treatments. [Clin Transplant] Abstract Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field. | |
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SCIENCE NEWSFate Therapeutics Announces Five Presentations Fate Therapeutics, Inc. announced that Fate scientists and collaborators will present data highlighting the company’s iPSC product platform and its iPSC-derived cell product candidates. [Press release from Fate Therapeutics, Inc. discussing research to be presented at the American Society of Gene & Cell Therapy (ASGCT) 22nd Annual Meeting, Washington, DC] Press Release Adaptimmune Announces Oral Presentation of Allogeneic SPEAR T-Cell Program Adaptimmune Therapeutics plc announced an oral presentation by Dr. Jo Brewer, VP of Platform Sciences, summarizing data from Adaptimmune’s off-the-shelf SPEAR T-cell program. Its title: ‘Differentiating T-Cells from Human iPSCs to Create Off-The-Shelf SPEAR T-Cell Therapies’. [Press release from Adaptimmune Therapeutics plc discussing research presented at the American Society of Gene & Cell Therapy (ASGCT) 22nd Annual Meeting, Washington, DC] Press Release | |
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INDUSTRY NEWSExCellThera Inc. announced that the FDA has granted RMAT designation to its lead technology, ECT-001, in the treatment of hematologic malignancies. The RMAT designation is based on strong data from Phase I/II clinical trials using ECT-001 to expand stem and immune cells for the treatment of blood cancers. [ExCellThera Inc.] Press Release Cell Microsystems Receives New NIH Grants for Automating CRISPR Workflows Cell Microsystems announced it has received two NIH Small Business Innovation and Research awards totaling $1.9M to automate CRISPR workflows using its proprietary CellRaft Technology. [Cell Microsystems (Business Wire, Inc.)] Press Release | |
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POLICY NEWSAfter Firings, MD Anderson Officials Try to Calm Fears of Racial Profiling Administrators at the MD Anderson Cancer Center in Houston, Texas, tried to reassure alarmed employees that its recent dismissals of faculty members alleged to have broken federal funding rules were not connected to race or ethnicity. [ScienceInsider] Editorial FDA Hires Pew Director to Lead Regulatory Policy Elizabeth Jungman, a well-known public health expert and a Capitol Hill veteran, will lead the FDA’s regulatory policy office starting this summer, STAT has learned. Jungman, who currently serves as head of public health programs at the Pew Charitable Trusts, will direct the FDA’s Office of Regulatory Policy, a post with sweeping authority over FDA’s human drugs portfolio, two sources told STAT. [STAT] Editorial
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EVENTSNEW FEBS: From Molecules to Living Systems Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Research Assistant – Stem Cells & Regenerative Medicine (Boston Children’s Hospital) Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.) Scientist – Cell Culture Media and Cell Line Development (STEMCELL Technologies Inc.) Postdoctoral Lecturer – Stem Cell Biology & Regenerative Medicine (The University of Manchester) Postdoctoral Fellowship – iPSCs and Differentiated Neurons (Howard Hughes Medical Institute) Associate Staff Scientist, Automation Systems (New York Stem Cell Foundation) Director of Operations – Biotech Production (Cincinnati Children’s Hospital Medical Center) Postdoctoral Fellowship – Patient-Derived iPSC Research (Oklahoma Medical Research Foundation) Postdoctoral Fellowship – Human iPSC Research (Emory University) Postdoctoral Fellow – Genetics and Epigenomics of iPSC Biology (Stanford University) Assistant Associate Professor/Professor in Residence – Stem Cell Program (UC 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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