ESC & iPSC News 14.13 April 11, 2019 | |
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TOP STORYScientists demonstrated the feasibility of using type I CRISPR-Cas to effectively introduce a spectrum of long-range chromosomal deletions with a single RNA guide in human embryonic stem cells and HAP1 cells. Type I CRISPR systems relied on the multi-subunit ribonucleoprotein complex Cascade to identify DNA targets and on the helicase-nuclease enzyme Cas3 to degrade DNA processively. [Mol Cell] Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Bromodomain Inhibition of the Coactivators CBP/EP300 Facilitate Cellular Reprogramming To uncover pathways that maintain cell identity, researchers performed a reprogramming screen using inhibitors of chromatin factors. They identified acetyl-lysine competitive inhibitors targeting the bromodomains of coactivators cyclic-AMP response element binding protein binding protein (CBP) and E1A binding protein of 300-kDa (EP300) as potent enhancers of reprogramming. [Nat Chem Biol] Abstract Regeneration of a Bioengineered 3D Integumentary Organ System from iPS Cells Investigators described how to induce the differentiation of murine iPSCs into a 3D-integumentary organ system. First, iPSCs were grown for seven days under conditions that encourage the formation of embryoid bodies (EBs). The iPSC-derived EBs were stimulated by Wnt10b one day before transplantation of multiple EBs in vivo. [Nat Protoc] Abstract Oncogenic PIK3CA Promotes Cellular Stemness in an Allele Dose-Dependent Manner To determine the consequences of genetic PIK3CA activation in a developmental context of relevance to both PROS and cancer, the authors engineered isogenic human iPSCs with heterozygous or homozygous knockin of PIK3CAH1047R. While heterozygous iPSCs remained largely similar to wild-type cells, homozygosity for PIK3CAH1047R caused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, up-regulation of stemness markers, and impaired differentiation to all three germ layers in vitro and in vivo. [Proc Natl Acad Sci USA] Full Article Genome-Scale CRISPR Screens Identify Human Pluripotency-Specific Genes Scientists developed a scalable and renewable Cas9 and sgRNA-human PSC library in which loss-of-function mutations could be induced at will. This inducible mutant human PSC library could be used for multiple genome-wide CRISPR screens in a variety of hPSC-induced cell types. [Cell Rep] Full Article To map essential genetic determinants of hPSC fitness, investigators performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify essential genes. Among these, they found FOXH1 and VENTX, genes that encoded transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. [Cell Rep] Full Article | Graphical Abstract Fluorescent Gene Tagging of Transcriptionally Silent Genes in hiPSCs A monomeric EGFP fusion tag and a constitutively expressed mCherry fluorescence selection cassette were delivered in tandem via homology-directed repair to five genes not expressed in hiPSCs but important for cardiomyocyte sarcomere function: TTN, MYL7, MYL2, TNNI1, and ACTN2. CRISPR/Cas9 was used to deliver the selection cassette and subsequently mediate its excision via microhomology-mediated end-joining and non-homologous end-joining. [Stem Cell Reports] Full Article Micrococcal nuclease sequencing revealed increased enrichment of nucleosomes around transcriptional start site regions and DNase I hypersensitive sites in KDM5B-depleted ESCs. Moreover, depletion of KDM5B resulted in a widespread redistribution and disorganization of nucleosomes in a sequence-dependent manner. [Epigenetics Chromatin] Full Article Researchers examined the potential effects of bisphenol A, bisphenol F, and bisphenol S on embryonic development with an in vitro stem cell toxicology system and transcriptomics analyses. Mouse ESCs were differentiated via embryoid body formation, either globally towards the three primary germ layers and their lineages, or specifically into neuroectoderm/neural progenitor cells. [Ecotoxicol Environ Saf] Abstract | Graphical Abstract Correction of NR2E3 Associated Enhanced S-Cone Syndrome Patient-Specific iPSCs Using CRISPR-Cas9 Scientists developed a CRISPR-based homology-directed repair strategy and corrected two different disease-causing NR2E3 mutations in patient-derived iPSCs generated from two affected individuals. In addition, one patient’s iPSCs were differentiated into retinal cells and NR2E3 transcription was evaluated in CRISPR corrected and uncorrected clones. [Ecotoxicol Environ Saf] Full Article Subscribe to one of our other 19 science newsletters such as Cell Therapy News & Mesenchymal Cell News. | |
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REVIEWSPolycomb/Trithorax Antagonism: Cellular Memory in Stem Cell Fate and Function The authors draw from embryonic and adult stem cell studies to discuss the complex roles played by Polycomb group and Trithorax group proteins in maintaining cell identity while allowing for microenvironment-mediated alterations in cell fate. Finally, they discuss the potential for targeting these proteins as a therapeutic approach in cancer. [Cell Stem Cell] Abstract Human Pluripotent Stem Cell-Derived Cardiomyocytes for Studying Energy Metabolism Investigators review the physiological drivers of metabolic maturation and concentrate on methods to mature human iPSC-cardiomyocytes (hiPSC-CMs) with the goal to benchmark the metabolic state of hiPSC-CM against in vivo data and to see how far known abnormalities in inherited metabolic disorders can be modeled in hiPSC-CM. [Biochim Biophys Acta] Abstract Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field. | |
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INDUSTRY NEWSEditas Medicine, Inc. announced a strategic research collaboration and cross-licensing agreement to combine their respective genome editing and cell therapy technologies to discover, develop, and manufacture novel engineered cell medicines. [Edita Medicine, Inc.] Press Release UConn and Foundation for Prader-Willi Research Create Stem Cell Biobank A new collaboration between UConn Health and the Foundation for Prader-Willi Research will create a centralized, high quality biobank of stem cells to help researchers better understand Prader-Willi syndrome, a rare genetic disease that may hold insights into obesity, developmental delays, autism spectrum disorders, and many other conditions. [University of Connecticut] Press Release | |
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POLICY NEWSRacism Rife at Top South African University, Says Report A damning report that says racism is entrenched at the University of Cape Town has reignited discussions about how to erase the divisive legacy of colonialism at South Africa’s top research institutions. [Nature News] Editorial FDA, New York Attorney General Go After Stem Cell Clinics On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist] Editorial Bioethicists Concerned over Japan’s Chimera Embryo Regulations Japanese regulators have effectively given the green light to research involving human-animal chimera embryos. Many researchers see the move to relax the rules as a welcome change, yet some are worried the revisions don’t take public concerns enough into consideration. [The Scientist] Editorial
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EVENTSNEW Gordon Research Conference: Metalloproteases Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellowship – iPSCs and Differentiated Neurons (Howard Hughes Medical Institute) Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.) Scientist – Cell Culture Media and Cell Line Development (STEMCELL Technologies Inc.) 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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