ESC & iPSC News Volume 14.23 | Jun 19 2019

TOP STORY

Myc 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

(Ranked by impact factor of the journal)

Hypoxia-Enhanced Blood-Brain Barrier Chip Recapitulates Human Barrier Function and Shuttling of Drugs and Antibodies

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

Epiblast Formation by TEAD-YAP-Dependent Expression of Pluripotency Factors and Competitive Elimination of Unspecified Cells

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

Id1 Stabilizes Epiblast Identity by Sensing Delays in Nodal Activation and Adjusting the Timing of Differentiation

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

Specific Contributions of Cohesin-SA1 and Cohesin-SA2 to TADs and Polycomb Domains in Embryonic Stem Cells

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

Embryonic Stem Cell Microenvironment Suppresses the Malignancy of Cutaneous Melanoma Cells by Down-Regulating PI3K/AKT Pathway

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

The Depletion of p38alpha Kinase Upregulates NADPH Oxidase 2/NOX2/gp91 Expression and the Production of Superoxide in Mouse Embryonic Stem Cells

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

Biomimetic Modification of Dual Porosity poly(2-Hydroxyethyl Methacrylate) Hydrogel Scaffolds – Porosity and Stem Cell Growth Evaluation

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

The Ubiquitin Proteasome System Is a Key Regulator of Pluripotent Stem Cell Survival and Motor Neuron Differentiation

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

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Organoids-on-a-Chip

As 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.

New 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’ Allogeneic Cell Therapy Product, ALLOB, Meets Primary Endpoints in Phase IIa Study in Patients Undergoing a Lumbar Spinal Fusion Procedure

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

US 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

NEW The New York Stem Cell Conference Foundation Conference
October 22-23, 2019
New York, New York, United States

Visit our events page to see a complete list of events in the community.

NEW 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)

Postdoctoral Fellow – Stem Cells and Regenerative Medicine (German Research Center for Environmental Health)

Postdoctoral Associate – Stem Cell Differentiation in Immunology (University of Massachusetts Medical School)

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)

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