ESC & iPSC News Volume 13.08 | Feb 28 2018

TOP STORY

Missing Link Found between Pathways Involved in Cell Development

A new mechanism that coordinates human development in response to signals from outside the cell has been discovered by researchers. The study revealed that the SMAD2 and SMAD3 proteins link and coordinate many different pathways in the cell that were previously believed to be separate. [Press release from the Wellcome Sanger Institute discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

RNA-Dependent Chromatin Targeting of TET2 for Endogenous Retrovirus Control in Pluripotent Stem Cells

Investigators showed that ten-eleven translocation (TET) 2 is recruited by the RNA-binding protein paraspeckle component 1 through transcriptionally active loci, including endogenous retroviruses whose long terminal repeats have been co-opted by mammalian genomes as stage- and tissue-specific transcriptional regulatory modules. [Nat Genet] Abstract

Purkinje Cells Derived from TSC Patients Display Hypoexcitability and Synaptic Deficits Associated with Reduced FMRP Levels and Reversed by Rapamycin

The authors developed a cerebellar Purkinje cell model of tuberous sclerosis complex (TSC) with patient-derived human iPSCs to characterize the molecular mechanisms underlying cerebellar abnormalities in autism spectrum disorder and TSC. [Mol Psychiatry] Abstract | Press Release

High-Efficiency RNA-Based Reprogramming of Human Primary Fibroblasts

Scientists showed that the synergistic activity of synthetic modified mRNAs encoding reprogramming factors and miRNA-367/302s delivered as mature miRNA mimics greatly enhances the reprogramming of human primary fibroblasts into iPSCs. [Nat Commun] Full Article | Press Release

Prostaglandin E₂ Is Required for BMP4-Induced Mesoderm Differentiation of Human Embryonic Stem Cells

The authors demonstrated the requirement of a bioactive lipid, prostaglandin E₂ (PGE₂), for the mesoderm specification from human ESCs by bone morphogenetic protein 4 (BMP4) induction. They showed that BMP4 directly regulates the expression of the key enzyme for PGE₂ synthesis, COX–1, and promotes PGE₂ production. [Stem Cell Reports] Full Article

TGFβ Signaling Hyperactivation-Induced Tumorigenicity during the Derivation of Neural Progenitors from Mouse ESCs

Researchers differentiated Oct4-GFP mouse ESCs into neural progenitor cells and found that a minority of Oct4⁺ cells are continuously sustained at Oct4⁺ state. The differentiation potential of these enriched cells was tightly restricted with much higher tumorigenic activity, which were thus defined as differentiation-resistant ESCs. [J Mol Cell Biol] Abstract

Suppression of the ERK-SRF Axis Facilitates Somatic Cell Reprogramming

Scientists generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. [Exp Mol Med] Full Article

Immunologic Targeting of CD30 Eliminates Tumorigenic Human Pluripotent Stem Cells, Allowing Safer Clinical Application of hiPSC-Based Cell Therapy

Investigators hypothesized that brentuximab vedotin, which targets CD30, induces apoptosis in tumorigenic cells, thus increasing the safety of iPSC therapy for heart failure. Brentuximab vedotin significantly reduced Lin28 expression in cardiomyogenically differentiated human iPSCs. [Sci Rep] Full Article

Vasopressin-Secreting Neurons Derived from Human Embryonic Stem Cells through Specific Induction of Dorsal Hypothalamic Progenitors

Researchers established the differentiation method for arginine-vasopressin (AVP)-secreting neurons from human ESCs by recapitulating in vitro and the in vivo embryonic developmental processes of AVP neurons. At first, the differentiation efficiency was improved. That was achieved through the optimization of the culture condition for obtaining dorsal hypothalamic progenitors. [Sci Rep] Full Article

New Considerations for hiPSC-Based Models of Neuropsychiatric Disorders

The authors discuss recent advances in psychiatric genomics and post-mortem studies that provide critical insights concerning cell-type composition and sample size that should be considered when designing human iPSC (hiPSC)-based studies of complex genetic disease. [Mol Psychiatry] Abstract

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

Fate Therapeutics Announces Receipt of CIRM Grant for Clinical Translation of FT516 Off-the-Shelf Engineered NK Cell Cancer Immunotherapy

Fate Therapeutics, Inc. announced that the California Institute for Regenerative Medicine (CIRM) awarded the company a $4.0 million grant to advance FT516 into a first-in-human clinical trial. The NK cell product candidate is derived from a clonal master iPSC line engineered to uniformly express a novel CD16 Fc receptor. [Fate Therapeutics, Inc.] Press Release

When Aging Goes Wrong: Researchers Try to Identify Causes of Alzheimer’s

David Brafman, an assistant professor of biomedical engineering at Arizona State University’s Ira A. Fulton Schools of Engineering, partnered with Mayo Clinic’s Dr. Richard J. Caselli to use a stem-cell-based approach to identify causes of Alzheimer’s disease in people with various levels of risk based on variations of the apolipoprotein E gene. [Arizona State University] Press Release

Canadian Science Wins Billions in New Budget

Canadian Prime Minister Justin Trudeau’s administration released its 2018 budget and scientists couldn’t be happier. It includes almost CAD 4 billion (USD 3.1 billion) in new funding for science over the next five years, a significant portion of which will go to the country’s three granting councils. [Nature News] Editorial

Europe’s Influential Science-Policy Chief on His Successes and Disappointments

Robert-Jan Smits is about to stand down from one of the most important science-policy jobs in Europe. After eight years, he will hand over his role as director-general of the European Commission’s research directorate to Jean-Eric Paquet, currently a deputy-secretary-general at the commission. [Nature News] Editorial

Here’s How the Scientists Running for Office Are Doing

They’re trained problem-solvers, but they have to learn to move beyond data to run successful campaigns. [The Atlantic] Editorial

Indian Scientist’s Sacking Spotlights Sexual Harassment

Female scientists in India hope that more academics will report sexual harassment without fear of jeopardizing their career or reputation, after a prominent biologist was sacked for allegedly harassing a staff member. [Nature News] Editorial

Merkel Makes a Surprise Pick for German Research Minister

German Chancellor Angela Merkel isn’t known for her political surprises. But she managed a big one when she tapped Anja Karliczek, a 46-year-old lawmaker little known outside of party circles, as Germany’s next minister for education and research. [ScienceInsider] Editorial

NEW Stem Cells in Disease Modeling and Drug Discovery (SCDMDD) 2018
June 17-18, 2018
Melbourne, Australia

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

NEW Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

NEW Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University)

NEW Postdoctoral Fellow – Neurodegenerative Diseases (University of Alabama at Birmingham)

Principal Investigator – Stem Cell Approaches to Study Neurodevelopmental Diseases (CHU Sainte-Justine, University of Montreal)

Postdoctoral Associate – Induced Pluripotent Stem Cells (Duke University)

Postdoctoral Fellow – Stem Cell Biology (City of Hope)

Postdoctoral Position – Metabolic Regulation of Embryos and Stem Cells (Joslin Diabetes Center)

Associate Scientific Editor – Cell Reports/Cell Stem Cell (Elsevier)

Postdoctoral Position – Pancreas Development and Stem Cells (Helmholtz Zentrum München)

Postdoctoral Fellowship – Neurodegeneration (Lund University)

Research Scientist – Stem Cell Research (Evotec AG)

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