ESC & iPSC News 14.23 June 19, 2019 | |
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TOP STORYMyc and Dnmt1 Impede the Pluripotent to Totipotent State Transition in Embryonic Stem Cells To understand how this transition takes place, researchers performed single-cell RNA-seq, which revealed a two-step transcriptional reprogramming process characterized by downregulation of pluripotent genes in the first step and upregulation of the two-cell-embryo-specific elements in the second step. To identify factors controlling the transition, they performed a CRISPR-Cas9-mediated screen, which revealed Myc and Dnmt1 as two factors preventing the transition. [Nat Cell Biol] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)The authors describe an in vitro microfluidic organ-on-a-chip blood-brain barrier (BBB) model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulated the high level of barrier function of the in vivo human BBB for at least one week in culture. [Nat Commun] Full Article Scientists examined the mechanisms of epiblast formation and found that the Hippo pathway transcription factor TEAD and its coactivator YAP regulated expression of pluripotency factors. After specification of the inner cell mass, YAP accumulated in the nuclei and activated TEAD. [Dev Cell] Full Article | Graphical Abstract Investigators report that Id1 acted as a sensor to detect delays in Nodal activation after the downregulation of Nanog. Id1 then suppressed fibroblast growth factor activity to delay differentiation. Accordingly, Id1 was not required for naive or primed pluripotency but rather stabilized epiblast identity during the transition between these states. [Dev Cell] Full Article | Graphical Abstract ZIC3 Controls the Transition from Naive to Primed Pluripotency Researchers investigated the early events in this transition by determining the changes in the open chromatin landscape as naive mouse ESCs transitioned to epiblast-like cells. Motif enrichment analysis of the newly opening regions coupled with expression analysis identified ZIC3 as a potential regulator of this cell fate transition. [Cell Rep] Full Article | Graphical Abstract The authors found that cohesin-SA2 facilitated Polycomb domain compaction through Polycomb repressing complex 1 recruitment and promoted the establishment of long-range interaction networks between distant Polycomb-bound promoters that are important for gene repression. Cohesin-SA1, in contrast, disrupted these networks, while preserving topologically associating domain (TAD) borders. [Cell Rep] Full Article | Graphical Abstract Functional Roles of hnRNPA2/B1 Regulated by METTL3 in Mammalian Embryonic Development Scientists found that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) was crucial for early embryonic development by virtue of regulating specific gene transcripts. HnRNPA2/B1 was localized to the nucleus and cytoplasm during subsequent embryonic development, starting at fertilization. Knockdown of hnRNPA2/B1 delayed embryonic development after the four-cell stage and blocked further development. [Sci Rep] Full Article Researchers investigated a better method and the mechanism of ESC microenvironment supplied by ESCs on suppressing the malignancy of cutaneous melanoma cells. Cutaneous melanoma cell line A2058 was cultured and divided into four groups: A2058-only; A2058 and ESCs continuously co-cultured (Group One); A2058 co-cultured with daily refreshed ESCs; Group One with VO-Ohpic, inhibitor of PTEN. [Cancer Med] Full Article Investigators report that p38alpha kinase-deficient ESCs exhibited a higher production of reactive oxygen species (ROS) in contrast to their wild-type counterpart. Analysis of the expressions of NADPH oxidases and dual oxidases, crucial enzymes involved in intracellular ROS formation, showed NOX2/gp91phox was over-expressed in p38alpha deficient cells. [Arch Biochem Biophys] Abstract The morphological microstructure of hydrogels was characterized in the gel swollen state and the susceptibility of gels for stem cells was evaluated. The effect of specific chemical groups covalently bound in the hydrogel network by copolymerization on cell adhesion and growth, followed by the effect of laminin coating was investigated. [Biomed Mater] Abstract Scientists sought to map the changing ubiquitome in human iPSCs during their pluripotent stage and following differentiation to motor neurons. Ubiquitinomics analysis identified that spliceosomal and ribosomal proteins were more ubiquitylated in pluripotent stem cells, whilst proteins involved in fatty acid metabolism and the cytoskeleton were specifically ubiquitylated in the motor neurons. [Cells] Full Article | Graphical Abstract Subscribe to one of our other 19 science newsletters such as Cell Therapy News & Mesenchymal Cell News. | |
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REVIEWSAs organoid technology opens up new frontiers of research in biomedicine, there is an emerging need for innovative engineering approaches for the production, control, and analysis of organoids and their microenvironment. The authors explore organ-on-a-chip technology as a platform to fulfill this need and examine how this technology may be leveraged to address major technical challenges in organoid research. They also discuss emerging opportunities and future obstacles for the development and application of organoid-on-a-chip technology. [Science] Abstract The Role of 3D Genome Organization in Development and Cell Differentiation Investigators discuss recent progress in the understanding of the general principles of chromatin folding, its regulation and its functions in mammalian development. Specifically, they discuss the dynamics of 3D chromatin and genome organization during gametogenesis, embryonic development, lineage commitment and stem cell differentiation, and focus on the functions of chromatin architecture in transcription regulation. [Nat Rev Mol Cell Biol] Abstract Mechanisms, Hallmarks, and Implications of Stem Cell Quiescence Scientists discuss recent advances uncovering intracellular signaling pathways, transcriptional changes, and extracellular cues within the stem cell niche that control induction and exit from quiescence in tissue stem cells. They discuss the implications of quiescence as well as the pharmacological and genetic approaches that are being explored to either induce or prevent quiescence as a therapeutic strategy. [Stem Cell Reports] Full Article Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field. | |
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INDUSTRY NEWSNew CRISPR Lab to Accelerate Drug Discovery, Advance Genomic Research GlaxoSmithKline plc has launched a five-year, $67 million collaboration with the San Francisco and Berkeley campuses of the University of California to build a state-of-the-art laboratory that will use CRISPR technologies to explore how genes cause disease and to rapidly accelerate the discovery of new medicines. [University of California, San Francisco] Press Release Bone Therapeutics announced that its allogeneic cell therapy product, ALLOB, successfully completed the 12 months follow-up period of a Phase IIa study in patients undergoing a lumbar spinal fusion procedure. [Bone Therapeutics] Press Release | |
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POLICY NEWSUS House Moves to Block New Reviews of Fetal Tissue Research In the wake of an announcement that research using fetal tissue at the National Institutes of Health will halt, and that other federally funded research using the tissue will now require review by ethics advisory boards, the US House voted on June 13 to include an amendment in the 2020 federal budget that would prevent such boards from being formed. [The Scientist] Editorial Academics Join Outcry Sparked by Hong Kong’s Contentious Extradition Bill Since the bill that would legalize the extradition of people from Hong Kong to mainland China to stand trial or serve criminal sentences was announced, more than a thousand academics from around the world have signed a petition against the proposed law, saying it would restrict free speech and academic debate as well as eroding personal freedoms. [Nature News] Editorial Men Need Not Apply: University Set to Open Jobs Just to Women A Dutch engineering university is taking radical action to increase its share of female academics by opening job vacancies to women only. Starting on 1 July, the Eindhoven University of Technology in the Netherlands will not allow men to apply for permanent academic jobs for the first six months of the recruitment process under a new fellowship program. [Science Magazine] Editorial
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EVENTSNEW The New York Stem Cell Conference Foundation Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Postdoctoral Fellows – Striated Muscle Regeneration (Duke University) Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.) Postdoctoral Fellow – iPSC Models of Diabetes (New York Stem Cell Foundation) Research Technichian – iPSC Generation and Differentiation (The University of Chicago) Postdoctoral Researcher – Cystic Fibrosis Stem Cell Models (The University of Alabama at Birmingham) Postdoctoral Researcher – Dementia Treatment with iPSCs (Cardiff University) Postdoctoral Associate – RNA Genomics in iPSCs (The Jackson Laboratory) Research Assistant – Stem Cells & Regenerative Medicine (Boston Children’s Hospital) Postdoctoral Fellow – Pluripotent Stem Cells & Joint Tissue Development (Boston Children’s Hospital) 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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