ESC & iPSC News Volume 8.22 | Jun 5 2013

MBNL Proteins Repress ES-Cell-Specific Alternative Splicing and Reprogramming
Alternative splicing represents a widely acting mode of gene regulation, yet its role in regulating embryonic stem (ES)-cell pluripotency and differentiation is poorly understood. Researchers identified the muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of cassette exon alternative splicing events that are differentially regulated between ES cells and other cell types. [Nature] Abstract

Rapid Single-Step Induction of Functional Neurons from Human Pluripotent Stem Cells
Researchers showed that human embryonic stem cells and induced pluripotent cells can be converted into functional induced neuronal cells with nearly 100% yield and purity in less than two weeks by forced expression of a single transcription factor. [Neuron] Abstract | Full Article

Identification of Small Molecules for Human Hepatocyte Expansion and iPS Differentiation
Scientists developed a high-throughput screening platform for primary human hepatocytes to identify small molecules in two different classes that can be used to generate renewable sources of functional human hepatocytes. The first class induced functional proliferation of primary human hepatocytes in vitro. The second class enhanced hepatocyte functions and promoted the differentiation of induced pluripotent stem (iPS) cell-derived hepatocytes toward a more mature phenotype than what was previously obtainable. [Nat Chem Biol] Abstract | Press Release

Genome-Wide Kinase-Chromatin Interactions Reveal the Regulatory Network of ERK Signaling in Human Embryonic Stem Cells
Investigators studied the convergence of the extracellular signal-regulated kinase (ERK) signaling cascade at the DNA by mapping genome-wide kinase-chromatin interactions for ERK2 in human embryonic stem cells. [Mol Cell] Abstract | Graphical Abstract

Abnormal Neuronal Differentiation and Mitochondrial Dysfunction in Hair Follicle-Derived Induced Pluripotent Stem Cells of Schizophrenia Patients
Induced pluripotent stem cells (iPSCs) from three schizophrenia patients and from two controls were reprogrammed from hair follicle keratinocytes, because of their accessibility and common ectodermal origin with neurons. iPSCs were differentiated into Pax6⁺/Nestin⁺ neural precursors and then further differentiated into β3-Tubulin⁺/tyrosine hydroxylase⁺/DAT⁺ dopaminergic neurons. [Mol Psychiatry] Abstract

The Aryl Hydrocarbon Receptor Directs Hematopoietic Progenitor Cell Expansion and Differentiation
Using a novel, iPSC-based, chemically-defined, serum and feeder cell-free culture system, the authors showed that a functional aryl hydrocarbon receptor (AhR) is expressed in hematopoietic progenitor cells (HPs), and that remarkably, AhR activation in these HPs drives an unprecedented expansion of HPs, megakaryocyte- and erythroid-lineage cells. [Blood] Abstract | Press Release

Identification of Unsafe Human Induced Pluripotent Stem Cell Lines Using a Robust Surrogate Assay for Pluripotency
Investigators reported that virally derived human induced pluripotent stem cells (hiPSC), but not human embryonic stem cells (hESC) or hiPSC derived using episomal non-integrating vectors, exhibit a propensity to revert to a pluripotent phenotype following differentiation. This instability was revealed using their published method to identify pluripotent cells undergoing very early-stage differentiation in standard hESC cultures, by fluorescence activated cell sorting based on expression of the cell surface markers TG30 and GCTM-2. [Stem Cells] Abstract | Press Release

Human Stem Cell-Based Three-Dimensional Microtissues for Advanced Cardiac Cell Therapies
Scientists compared clinically relevant, human stem cell sources for their ability to generate three-dimensional microtissues (3D-MTs) with particular regards to formation characteristics, proliferation-activity, viability and extracellular-matrix production. Single-cell suspensions of human bone marrow- and adipose tissue-derived mesenchymal stem cells, Isl1⁺ cardiac progenitors derived from human embryonic stem cells, and undifferentiated human induced pluripotent cells were characterized before to generate 3D-MTs using a hanging-drop culture. [Biomaterials] Abstract

Ten-Eleven Translocation 1 (Tet1) Is Regulated by O-GlcNAc Transferase (Ogt) for Target Gene Repression in Mouse Embryonic Stem Cells
To understand how Tet1 may regulate gene expression, researchers conducted large-scale immunoprecipitation followed by mass spectrometry of endogenous Tet1 in mouse embryonic stem cells. [J Biol Chem] Abstract | Full Article

WNT3 Is a Biomarker Capable of Predicting the Definitive Endoderm Differentiation Potential of hESCs
Investigators report identification of WNT3 as a biomarker capable of predicting definitive endoderm (DE) differentiation potential of human embryonic stem cells (hESCs). They showed that the mRNA level of WNT3 in hESCs correlates with their DE differentiation efficiency. [Stem Cell Rep]
Abstract | Full Article | Press Release

The Mechanisms of Hedgehog Signaling and its Roles in Development and Disease
The cloning of the founding member of the Hedgehog (HH) family of secreted proteins two decades ago inaugurated a field that has diversified to encompass embryonic development, stem cell biology and tissue homeostasis. Interest in HH signaling increased when the pathway was implicated in several cancers and congenital syndromes. [Nat Rev Mol Cell Biol] Abstract

Embryonic Stem Cells as a Treatment for Macular Degeneration
The authors present the pathophysiologic case for retinal pigment epithelium transplantation with stem cell-derived tissue, a review of the preclinical data substantiating the hypothesis and the initial clinical trials safety data from early human trials. [Expert Opin Biol Ther] Abstract

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

Two Researchers Named Shaw Scientists
The Greater Milwaukee Foundation has chosen two University of Wisconsin-Madison researchers for 2013 Shaw Scientist Awards. Each Shaw Scientist receives $200,000 in unrestricted research support. Goldsmith, who works to immobilize single molecules to study the way they move and change shape, will apply his Shaw award funding to research on a protein called tau. Sridharan examines the ways cells can be reprogrammed to serve different functions. [University of Wisconsin-Madison] Press Release

Licenses Granted for the Manufacture of Human Cell Therapy Products
Roslin Cells Ltd, the Scottish National Blood Transfusion Service and the University of Edinburgh announced that the GMP Cellular Therapy Manufacturing Facility within the Scottish Centre for Regenerative Medicine has recently been licensed by the Medicines and Healthcare products Regulatory Agency for the manufacture of human cell therapy products. [Scottish National Blood Transfusion Service] Press Release

Top European Life Science Institutes Join Forces
Ten top European life sciences institutes have launched a new alliance to help themselves become more competitive and have a strong, unified voice in European science policy. [EU-Life, European Union]
Press Release

Japan Aims High for Growth
Prime Minister Shinzo Abe is riding high since his Liberal Democratic Party swept back to power. He has stimulated the economy, ending 15 years of deflation, jumpstarted the stock market and weakened the yen to spur exports. His reform platform includes a new growth strategy, and central to that strategy is innovation in science and technology. [Prime Minister, Japan] Press Release

Russian Academy of Sciences Elects Reformer as President
The Russian Academy of Sciences (RAS) has elected itself a new president. Yuri Osipov, who has headed RAS since the collapse of the Soviet Union, has stepped down and RAS members chose Vladimir Fortov, head of the RAS Joint Institute for High Temperatures in Moscow, to replace him. [Russian Academy of Sciences, Russia] Press Release

France's Message to Science: Help Us Fix the Economy
The National Assembly approved a new law that aims to simplify the national landscape for research and higher education and make it more efficient, better able to address societal and economic challenges, and more competitive at the European level. The bill, which comes hand in hand with a new strategic plan for France's research priorities, also gives the government a greater role in coordinating research. The bill and the road map have been sharply criticized by various groups of researchers and university professors. [National Assembly, France] Press Release

Research Funders Propose Steps to Promote Open Access
A group of research funding organizations from around the world put its weight behind open access to the scientific literature but stopped short of making concrete policy recommendations for its members. [Global Research Council] Press Release

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NEW Postdoctoral Fellow - Cancer Immunology (Medical University of South Carolina)

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Postdoctoral Research Fellowships - Embryonic Stem Cells, Epigenetics, and Gene Regulation (NIEHS, National Institutes of Health)

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