ESC & iPSC News Volume 11.48 | Dec 7 2016

TOP STORY

Mitochondrial Replacement in Human Oocytes Carrying Pathogenic Mitochondrial DNA Mutations

Investigators reported mitochondrial replacement therapies or technique outcomes in several families with common mitochondrial (mt)DNA syndromes. The mother’s oocytes were of normal quality and mutation levels correlated with those in existing children. Efficient replacement of oocyte mutant mtDNA was performed by spindle transfer, resulting in embryos containing >99% donor mtDNA. Donor mtDNA was stably maintained in embryonic stem cells derived from most embryos. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

A Balance between Elongation and Trimming Regulates Telomere Stability in Stem Cells

Scientists report that telomere length is determined by the balance between telomere elongation, which is mediated by telomerase, and telomere trimming, which is controlled by XRCC3 and Nbs1, homologous recombination proteins that generate single-stranded C-rich telomeric DNA and double-stranded telomeric circular DNA, respectively. [Nat Struct Mol Biol] Abstract | Press Release

Generating High-Purity Cardiac and Endothelial Derivatives from Patterned Mesoderm Using Human Pluripotent Stem Cells

To test the functionality of endothelial cells (ECs) at different stages of differentiation, scientists provide methods for assaying the blood-forming potential and de novo lumen-forming activity of ECs. This is the first protocol that provides a common platform for directed differentiation of cardiomyocytes and endothelial subtypes from human pluripotent stem cells. [Nat Protoc] Full Article

Tet Proteins Influence the Balance between Neuroectodermal and Mesodermal Fate Choice by Inhibiting Wnt Signaling

Researchers showed that mouse embryonic stem cells, either lacking ten-eleven translocation (Tet)3 alone or with triple deficiency of Tet1/2/3, displayed impaired adoption of neural cell fate and concomitantly skewed toward cardiac mesodermal fate. [Proc Natl Acad Sci USA] Abstract | Press Release

In Vitro Derivation and Propagation of Spermatogonial Stem Cell Activity from Mouse Pluripotent Stem Cells

The in vitro derivation and propagation of spermatogonial stem cells (SSCs) from pluripotent stem cells is a key goal in reproductive science. Researchers showed that when aggregated with embryonic testicular somatic cells (reconstituted testes), primordial germ cell-like cells induced from mouse embryonic stem cells differentiate into spermatogonia-like cells in vitro and were expandable as cells that resemble germline stem cells, a primary cell line with SSC activity. [Cell Rep] Full Article | Graphical Abstract

Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells

Investigators report the characterization of EZH2-deficient human embryonic stem cells (hESCs). H3K27me3 was lost upon EZH2 deletion, identifying an essential requirement for EZH2 in methylating H3K27 in hESCs, in contrast to its non-essential role in mouse ESCs. [Cell Rep] Full Article

Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs

Researchers performed bioinformatics of RNA-Seq and ChIP-seq pluripotency data sets for two replicate Asian and Hispanic-Latino ethnically diverse induced pluripotent stem cell (iPSC) lines that reveal differences in generation of contractile cardiomyocytes but similar and robust differentiation to multiple neural, pancreatic, and smooth muscle cell types. [Sci Rep] Full Article

Economic 3D-Printing Approach for Transplantation of Human Stem Cell-Derived β-Like Cells

Using finite element modeling of cellular oxygen diffusion-consumption and an in vitro culture system that allows for culture of devices at physiological oxygen levels, the authors identified cluster sizes that avoided severe hypoxia within three dimensional (3D)-printed devices and developed a microwell-based technique for resizing clusters within this range. [Biofabrication] Abstract

OTX2 Impedes Self–Renewal of Porcine iPS Cells through Downregulation of NANOG Expression

The transcription factor Otx2 acts as a negative switch in the regulation of transition from naive to primed pluripotency in mouse pluripotent stem cells. However, the molecular features and function of porcine OTX2 have not been well elucidated in porcine-induced pluripotent stem cells (piPSCs). By studying high-throughput transcriptome sequencing and interfering endogenous OTX2 expression, researchers demonstrated that OTX2 is able to downgrade the self-renewal of piPSCs. [Cell Death Discov] Full Article

Elimination of Proliferating Cells from CNS Grafts Using a Ki67 Promoter-Driven Thymidine Kinase

Pluripotent stem cell (PSC)-based cell therapy is an attractive concept for neurodegenerative diseases, but can lead to tumor formation. This is particularly relevant as proliferating neural precursors rather than postmitotic mature neurons need to be transplanted. Thus, safety mechanisms to eliminate proliferating cells are needed. Scientists propose a suicide gene approach, based on cell cycle-dependent promoter Ki67-driven expression of herpes simplex virus thymidine kinase. Investigators generated a PSC line expressing this construct and induced neural differentiation. [Mol Ther Methods Clin Dev] Full Article

Patient-Derived Induced Pluripotent Stem Cells in Cancer Research and Precision Oncology

The author discusses the main advantages and limitations of induced pluripotent stem cells modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organs-on-chips and patient-derived xenografts. [Nat Med] Abstract

Induced Pluripotent Stem Cells as a New Getaway for Bone Tissue Engineering: A Systematic Review

Researchers review the available literature on osteogenic potential of induced pluripotent stem cells and to discuss methods applied to enhance their osteogenic potential. [Cell Prolif] Abstract

A New Era of Disease Modeling and Drug Discovery Using Induced Pluripotent Stem Cells

The author describes the recent advances in human induced pluripotent stem cell based disease modeling and drug discovery and discuss the current challenges. [Arch Pharm Res] Abstract

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Kadimastem Announces Strategic Collaboration with Korean Biotech Company Corestem, Including a $7M Investment in Kadimastem

Kadimastem announces a strategic collaboration with Korean biotech company Corestem, including a $7 million investment in Kadimastem. Corestem is the only company in the world with a cell therapy treatment for ALS which has been approved for marketing by a regulatory authority. Under the collaboration agreement, the companies will conduct clinical trials on Kadimastem’s product, AstroRx^®, in Korea and the Asia-Pacific region. [Kadimastem] Press Release

Tenaya Therapeutics Launches with the Goal of Curing Heart Disease

A new biopharmaceutical company, Tenaya Therapeutics Inc., will build on discoveries in cardiovascular disease research made at the Gladstone Institutes, concentrating on regenerative medicine and drug discovery for heart failure. Tenaya is supported by a $50 million Series A financing from The Column Group. [Gladstone Institutes] Press Release

Stopgap Spending Bill Leaves US Scientists in Limbo

In what has become a year-end tradition in Washington DC, the US Congress is getting ready to approve a stopgap spending measure before it adjourns for the holidays. Many researchers are more worried about what might come after this temporary funding extension, if it is approved. When president-elect Donald Trump takes office, Republicans will control the White House and both houses of Congress — and their science priorities are very different from those of outgoing President Barack Obama, a Democrat. [Nature News] Editorial

Mexico Proposal to Ban Human-Embryo Research Would Stifle Science

Researchers are waiting to see whether Mexico’s legislature will approve an amendment to the national health law that would ban experiments with human embryos. The amendment is intended to regulate assisted reproduction, including the payment of surrogate mothers, donations to egg and sperm banks and the fertilization of more than three eggs at a time. But it would also ban the creation of human embryos for any purpose except reproduction and any research with existing human embryos. [Nature News] Editorial

CRISPR Heavyweights Battle in US Patent Court

Berkeley and its rival, the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, are each vying for the intellectual property underlying CRISPR–Cas9, which is adapted from a system that bacteria use to fend off viruses. During the hearing the US Patent and Trademark Office judges challenged Berkeley’s central claim: that once its researchers demonstrated that CRISPR–Cas9 could be used to edit DNA in bacteria, any reasonably skilled person could have adapted the technique for use in more complex cells. [Nature News] Editorial

Help Wanted: Canada Begins Search for Chief Science Adviser

Canada has officially launched its search for a chief government science adviser, fulfilling a campaign promise by Prime Minister Justin Trudeau. Science Minister Kirsty Duncan announced the move on 5 December, after spending the past year consulting scientists about the exact role that such an adviser should have. [Nature News] Editorial

NEW Stem Cells in Drug Discovery
March 6-7, 2017
Cambridge, United Kingdom

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NEW Postdoctoral Fellowship – 3D Genome Organizers in Development and Disease (Karolinska Institute)

NEW Postdoctoral Reseach – Epigenetics (Institut of Molecular Biology (IMB))

Postdoctoral Researcher – ESC/iPSC Differentiation (Helmholtz Association)

Faculty Researcher – Stem Cell Biology (Stanford University)

Postdoctoral Researcher – Developmental Biology (RIKEN)

Research Assistant – Human Germ Cell Biology (University of Cambridge)

NYSCF Investigator – Stem Cell And Neuroscience (New York Stem Cell Foundation)

Postdoctoral Fellow – Neural Stem/Progenitor Cells (University of California – San Francisco)

Postdoctoral Fellow – Pluripotent Stem Cells, Cartilage Development and Disease (Boston Children’s Hospital and Harvard Medical School)

Staff Scientist/Research Assistant II – Pluripotent Stem Cells and Cartilage Biology (Boston Children’s Hospital and Harvard Medical School)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow Position – Stem Cell Biology & Immunology (Toronto General Research Institute & McEwen Centre for Regenerative Medicine)

Postdoctoral Fellow – Pluripotent Stem Cell Technology (University of California, Davis)

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