ESC & iPSC News Volume 14.20 | May 29 2019

TOP STORY

Loss of DUX Causes Minor Defects in Zygotic Genome Activation and Is Compatible with Mouse Development

To characterize the role of DUX in zygotic genome activation, investigators generated Dux cluster knockout (KO) mouse lines. Unexpectedly, they found that both Dux zygotic KO and maternal and zygotic KO embryos could survive to adulthood despite showing reduced developmental potential. [Nat Genet] Abstract

(Ranked by impact factor of the journal)

The Bipartite TAD Organization of the X-Inactivation Center Ensures Opposing Developmental Regulation of Tsix and Xist

Researchers generated genomic inversions that swap the Xist/Tsix transcriptional unit and placed their promoters in each other’s topologically associating domain. They found that this led to a switch in their expression dynamics: Xist became precociously and ectopically upregulated, both in male and female pluripotent cells, while Tsix expression aberrantly persisted during differentiation. [Nat Genet] Abstract

OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome

The authors showed that human iPSCs (hiPSCs) derived from Down syndrome (DS) patients overproduced OLIG2⁺ ventral forebrain neural progenitors. As a result, DS hiPSC-derived cerebral organoids excessively produced specific subclasses of GABAergic interneurons and caused impaired recognition memory in neuronal chimeric mice. [Cell Stem Cell] Abstract | Graphical Abstract

Modeling Cardiovascular Risks of E-Cigarettes with Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells

Human iPSC- derived epithelial cells (ECs) and a high-throughput screening approach were used to assess endothelial integrity following exposure to six different e-liquids with varying nicotine concentrations and to serum from e-cigarette users. [J Am Coll Cardiol] Abstract | Graphical Abstract

RNA Targets Ribogenesis Factor WDR43 to Chromatin for Transcription and Pluripotency Control

Scientists elucidated an unexpected role of an essential ribogenesis factor, WDR43, as a chromatin-associated RNA-binding protein and release factor in modulating the polymerase (Pol) II activity for pluripotency regulation. WDR43 bound prominently to promoter-associated noncoding/nascent RNAs, occupied thousands of gene promoters and enhancers, and interacted with the Pol II machinery in ESCs. [Mol Cell] Abstract | Graphical Abstract

SR9009 Has REV-ERB–Independent Effects on Cell Proliferation and Metabolism

A conditional REV-ERBα/β double-deletion mouse model was generated and used to test the specificity of SR9009 and a related compound. SR9009 was found to exert REV-ERB–independent effects on proliferation, metabolism, and gene transcription in two different cell types depleted of REV-ERBs. [Proc Natl Acad Sci USA] Abstract

CD34⁺KLF4⁺ Stromal Stem Cells Contribute to Endometrial Regeneration and Repair

Mechanistic studies suggested that SENP1 deletion induced SUMOylation of ERα, which augmented ERα transcriptional activity and proliferative signaling in SM22α⁺CD34⁺KLF4⁺ cells. These cells then transdifferentiated into the endometrial epithelium. Scientists’ study revealed that CD34⁺KLF4⁺ stromal-resident stem cells directly contributef to endometrial regeneration, which was regulated through SENP1-mediated ERα suppression. [Cell Rep] Full Article | Graphical Abstract

Live-Cell Imaging Reveals Enhancer-Dependent Sox2 Transcription in the Absence of Enhancer Proximity

Researchers visualized the spatial organization and transcriptional output of the key pluripotency regulator Sox2 and its essential enhancer Sox2 Control Region (SCR) in living ESCs. They found that Sox2 and SCR showed no evidence of enhanced spatial proximity and that spatial dynamics of this pair was limited over tens of minutes. [eLife] Full Article

Derivation of Novel Naive-Like Porcine Embryonic Stem Cells by a Reprogramming Factor–Assisted Strategy

Investigators combined a traditional ESC culture method with reprogramming factors to assist the establishment of porcine naive-like ESCs. Pig embryonic fibroblasts were transfected with a tetracycline-inducible vector carrying four classic mouse reprogramming factors, followed by somatic cell nuclear transfer and culturing to the blastocyst stage. [FASEB J] Abstract

TCam-2 Cells Deficient for SOX2 and FOXA2 Are Blocked in Differentiation and Maintain a Seminoma-Like Cell Fate In Vivo

The authors identified SOX2 as a key factor activated upon BMP inhibition mediating the reprogramming process by regulating pluripotency, reprogramming and epigenetic factors. Indeed, CRISPR/Cas9 SOX2-deleted seminomas (TCam-2) cells were able to maintain a seminoma-cell fate in vivo for about six weeks, but after six weeks in vivo still small sub-populations initiated differentiation. [Cancers] Full Article

Engineering the Vasculature of Decellularized Rat Kidney Scaffolds Using Human Induced Pluripotent Stem Cell-Derived Endothelial Cells

Scientists report how to efficiently engineer the kidney vasculature of decellularized rat kidney scaffolds by using human iPSC (hiPSCs)-derived endothelial cells (ECs). In vitro, hiPSC-ECs responded to flow stress by acquiring an alignment orientation, and attached to and proliferated on the acellular kidney sections, maintaining their phenotype. [Sci Rep] Full Article

Cell Cycle Dynamics of Mouse Embryonic Stem Cells in the Ground State and during Transition to Formative Pluripotency

By performing live imaging experiments of mouse ESCs (mESCs) bearing cell cycle reporters, researchers showed that cells in the pluripotent ground state displayed a cell cycle structure comparable to that reported for mESCs in serum-based media. Upon release from self-renewal, the cell cycle was rapidly accelerated by a reduction in the length of the G1 phase and of the S/G2/M phases, causing an increased proliferation rate. [Sci Rep] Full Article

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Modeling Neuropsychiatric Disorders Using Human Induced Pluripotent Stem Cells

The authors review recent progress and challenges in differentiation paradigms for generating disease-relevant cells and recent studies of neuropsychiatric disorders using human PSC models where cellular phenotypes linked to disease have been reported. The use of iPSC-based disease models holds great promise for understanding disease mechanisms and supporting discovery of effective treatments. [Protein Cell] Full Article

The Use of iPSC Technology for Modeling Autism Spectrum Disorders

Taking advantage of patient-derived stem cells, researchers are now able to generate neurons, glial cells and brain organoids in vitro to model Autism Spectrum Disorders (ASDs). Investigators report data from different studies showing how iPSCs have been a critical tool to study the different phenotypes of ASDs. [Neurobiol Dis] Abstract

Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field.

FDA Approves Jakafi^® (Ruxolitinib) for the Treatment of Patients with Acute Graft-Versus-Host Disease

Incyte Corporation announced that the FDA has approved Jakafi^® for the treatment of steroid-refractory acute GVHD in adult and pediatric patients 12 years and older. Jakafi is the first and only FDA-approved treatment for this indication. [Incyte Corporation] Press Release

Athersys Announces Fast Track Designation from FDA for MultiStem^® Program for Acute Respiratory Distress Syndrome

Athersys, Inc. announced that its clinical program evaluating MultiStem^® cell therapy for the treatment of acute respiratory distress syndrome has received Fast Track designation from the FDA. [Athersys, Inc.] Press Release

Casma Therapeutics Receives Grant from Michael J. Fox Foundation to Support Parkinson’s Drug Development

Casma Therapeutics, Inc. announced receipt of a Therapeutic Pipeline Program research grant from The Michael J. Fox Foundation for Parkinson’s Research to support development of a novel class of drugs to treat Parkinson’s disease. The $370,000 grant will advance Casma’s research into drugs that activate the calcium channel TRPML1 to promote the cellular process of autophagy to clear a toxic protein from the brain [Casma Therapeutics, Inc.] Press Release

Here’s Why the Outcomes of This Week’s European Elections Are Good News for Science

Although populist and euroskeptic parties grew in last week’s elections for the European Parliament, the tsunami that EU supporters feared didn’t happen. That comes as a relief to many scientists, because several of the populist movements now on the rise in Europe appear to have little interest in science, flirt with antiscientific ideas, or have tried to curtail academic freedom. [ScienceInsider] Editorial

White House Sends Mixed Messages on 2020 Research Spending Bills

President Donald Trump doesn’t want Congress to boost the budgets of the National Institutes of Health or the National Science Foundation. But he has no objection to giving more research dollars to parts of the Department of Energy and NASA. [ScienceInsider] Editorial

IEEE, a Major Science Publisher, Bans Huawei Scientists from Reviewing Papers

A major scientific society has banned employees of Huawei, the Chinese communications giant, from reviewing submissions to its journals because of US government sanctions against the company. The New York City-based Institute of Electrical and Electronics Engineers (IEEE) told editors of its roughly 200 journals yesterday that it feared “severe legal implications” from continuing to use Huawei scientists as reviewers in vetting technical papers. [ScienceInsider] Editorial

Labor Agency Revisits Whether Graduate Students Can Unionize

Since 2016, graduate teaching and research assistants at private institutions have had legal protection to form unions thanks to a ruling by the National Labor Relations Board determining that the students qualify as employees. But that may soon change: The NLRB, which now has a Republican majority, announced last week that it will make a new rule regarding students’ employee status. [TheScientist] Editorial

NEW 7^th Annual German Stem Cell Network Conference
September 23-25, 2019
Berlin, Germany

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

NEW Postdoctoral Researcher – Dementia Treatment with iPSCs (Cardiff University)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

Postdoctoral Associate – RNA Genomics in iPSCs (The Jackson Laboratory)

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

Postdoctoral Lecturer – iPSCs in Neuronal Modeling (Great Ormond Street Institute of Child 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 Fellowship – Cell Fate and Cancer Initiation (University of Miami Miller School of Medicine)

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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