Volume 8.08 | Feb 27

ESC & iPSC News 8.08 February 27, 2013
ESC & iPSC News
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TOP STORY
Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aß and Differential Drug Responsiveness
Working with a group from Nagasaki University, a research group at the Center for iPS Cell Research and Application has successfully modeled Alzheimer’s disease (AD) using both familial and sporadic patient-derived induced pluripotent stem cells (iPSCs), and revealed stress phenotypes and differential drug responsiveness associated with intracellular amyloid ß (Aß) oligomers in AD neurons and astrocytes. [Press Release from Kyoto University discussing online prepublication in Cell Stem Cell]
Press Release |
Abstract | Graphical Abstract 

Gain Hands-On Training: Culture hPSCs and Differentiate to Definitive Endoderm or Neural Progenitor Cells
PUBLICATIONS (Ranked by impact factor of the journal)

Reprogramming Human Fibroblasts to Pluripotency Using Modified mRNA
The authors describe a stepwise protocol for the generation of modified mRNA-derived induced pluripotent stem cells from primary human fibroblasts, focusing on the critical parameters including medium choice, quality control, and optimization steps needed for synthesizing modified mRNAs encoding reprogramming factors and introducing these into cells over the course of 2-3 weeks to ensure successful reprogramming. [Nat Protoc] Abstract

PML Bodies Provides an Important Platform for the Maintenance of Telomeric Chromatin Integrity in Embryonic Stem Cells
Investigators demonstrated that α-thalassemia mental retardation X-linked and histone H3.3 co-localize with the telomeric DNA and associated proteins within the promyelocytic leukemia (PML) bodies in mouse embryonic stem cells. [Nucleic Acids Res] Full Article

Induction of Pluripotent Stem Cells from Primordial Germ Cells by Single Reprogramming Factors
The expression of reprogramming factors in primordial germ cells (PGCs) was analyzed. PGCs expressed Oct3/4, Sox2, and c-Myc but not Klf4. However, Klf2, Klf5, Essrb, or Essrg, which were expressed in PGCs, could compensate for Klf4 during somatic cell reprograming. [Stem Cells] Abstract

Insulin Inhibits Cardiac Mesoderm, Not Mesendoderm, Formation During Cardiac Differentiation of Human Pluripotent Stem Cells and Modulation of Canonical Wnt Signaling Can Rescue This Inhibition
The advent of human pluripotent stem cell technology and robust cardiac differentiation methods affords a unique opportunity to monitor the full course of cardiac induction in vitro. Investigators showed that stage-specific activation of insulin signaling strongly inhibited cardiac differentiation during a monolayer-based differentiation protocol that used transforming growth factor ß superfamily ligands to generate cardiomyocytes. [Stem Cells] Abstract

Myoblasts and Embryonic Stem Cells Differentially Engraft in a Mouse Model of Genetic Dilated Cardiomyopathy
The functional and architectural benefits of embryonic stem cells (ESC) and myoblasts (Mb) transplantations into infarcted myocardium have been investigated extensively. Scientists report that engrafted differentiated cells were consistently detected in myocardia of mice receiving Mb, whereas few or no cells were detected in the hearts of mice receiving ESC, except in two cases where teratomas were formed. [Mol Ther] Abstract

Proliferation Rate of Somatic Cells Affects Reprogramming Efficiency
The discovery of induced pluripotent stem (iPS) cells provides not only new approaches for cell replacement therapy, but also new ways for drug screening. However, the undefined mechanism and relatively low efficiency of reprogramming have limited the application of iPS cells. In an attempt to further optimize the reprogramming condition, scientists unexpectedly observed that removing c-Myc from the Oct-4, Sox-2, Klf-4, and c-Myc combination greatly enhanced the generation of iPS cells. [J Biol Chem] Abstract

Efficient Derivation of Lateral Plate and Paraxial Mesoderm Subtypes from Human Embryonic Stem Cells through GSKi-Mediated Differentiation
Scientists demonstrated that inhibition of glycogen synthase kinase-3 (GSK-3) is an essential first step towards efficient generation of the mesoderm. Under chemically defined conditions without additional growth factors/cytokines, short-term GSKi (GSK inhibitor) treatment effectively drives differentiation of human embryonic stem cells into the primitive streak, which can potentially commit towards the mesoderm when further supplemented with BMP4. [Stem Cells Dev] Abstract

Differentiation of Human Embryonic Stem Cells into Cells with Corneal Keratocyte Phenotype

Investigators sought to identify conditions inducing differentiation of pluripotent human embryonic stem (hES) cells to the keratocyte lineage. Neural differentiation of hES cell line WA01(H1) was induced by co-culture with mouse PA6 fibroblasts. [PLoS One] Full Article

Demarcation of Stable Subpopulations within the Pluripotent hESC Compartment
Human embryonic stem cells (hESCs) express REX1 transcripts but the distribution and properties of REX1 expressing cells have yet to be described. To address these questions, researchers used gene targeting in human ESCs to insert the fluorescent protein Venus and an antibiotic selection marker under the control of the endogenous REX1 transcription regulatory elements, generating a sensitive, selectable reporter of pluripotency. [PLoS One] Full Article

Discovery of Pluripotency Associated MicroRNAs in Rabbit Preimplantation Embryos and Embryonic Stem-Like Cells
Increasing experimental evidence implies an important regulatory role of microRNAs (miRNAs) during embryonic development and in embryonic stem cell biology. In the current study, scientists described and analyzed the expression profile of pluripotency-associated miRNAs in rabbit embryos and embryonic stem-like cells. [Reproduction] Abstract

Modeling Human Protein Aggregation Cardiomyopathy Using Murine Induced Pluripotent Stem Cells
To determine whether induced pluripotent stem cell (iPSC)-derived cardiomyocytes, a new experimental approach for human disease modeling, would be relevant to aggregation-prone disorders, researchers decided to exploit the existing transgenic mouse model to derive iPSCs from tail tip fibroblasts. Several iPSC lines were generated from transgenic (TG) and non-TG mice and validated for pluripotency. [Stem Cells Transl Med] Abstract

New: Directed Differentiation of Pluripotent Stem Cells: A Cell Stem Cell Poster

REVIEWS
The Multiple Roles for Sox2 in Stem Cell Maintenance and Tumorigenesis
The authors focus on the different roles for Sox2 in stem cell maintenance and its oncogenic roles in the context of signal transcription and microRNA regulation. They also review the main upstream and downstream targets of Sox2, which can be potentially used as therapeutic measures to treat cancer with abnormal levels of Sox2. [Cell Signal] Abstract
INDUSTRY NEWS

Gladstone Scientist Named Inaugural Winner of Breakthrough Prize in Life Sciences
Gladstone Institutes’ Senior Investigator Shinya Yamanaka, MD, PhD, is one of 11 medical researchers to win a new, high-profile $3 million award from a group of high-tech sponsors, including the founders of Facebook and Google. [Gladstone Institutes] Press Release

USC Launches Regenerative Medicine and Stem Cell Research Initiative
A new University of Southern California (USC) initiative has been introduced to support collaborative research in regenerative medicine and stem cell biology across the university, facilitating the critical move from basic research into clinical applications. [University of Southern California] Press Release

POLICY NEWS

Expanding Public Access to the Results of Federally Funded Research
In a policy memorandum, Office of Science and Technology Policy Director John Holdren has directed Federal agencies with more than $100 million in R&D expenditures to develop plans to make the published results of federally funded research freely available to the public within one year of publication and requiring researchers to better account for and manage the digital data resulting from federally funded scientific research. [Office of Science and Technology Policy, The White House, United States] Press Release

New Breakthrough Prize Awards Millions to Life Scientists
Eleven scientists became multimillionaires when they were named the first winners of the new Breakthrough Prize in Life Sciences. Each researcher, whose specialties include genetics, stem cells, and cancer, will receive $3 million dollars, more than twice the maximum amount of a Nobel Prize. [ScienceInsider]
Press Release

NIH Director, Senator Mikulski Warn of Sequester’s Impact on Biomedical Research
The National Institutes of Health (NIH) and a key supporter in Congress warned about the damage to biomedical research if $85 billion in automatic cuts to all federal agencies goes into effect. NIH Director Francis Collins and Senator Barbara Mikulski (D-MD) said the so-called sequestration would slow scientific progress, delay clinical trials, and put a generation of young researchers at risk if NIH’s $31 billion budget for this year is trimmed by $1.5 billion. [National Institutes of Health, United States] Press Release

EVENTS

NEW StemCONN 2013: Realizing the Promise 
April 4, 2013
New Haven, United States

NEW SMi’s Cell Culture 2013
July 3-4, 2013
London, United Kingdom

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

JOB OPPORTUNITIES

Postdoctoral Position – Cardiovascular Regenerative Therapies (University of California, Los Angeles)

Senior Postdoctoral Position (Vrije Universiteit Brussel, Department of Biology)

Postdoctoral Position – Stem Cell Biology (Stony Brook University Medical Center)

Postdoctoral Position – iPS Cells in CNS Diseases (AbbVie Deutschland GmbH & Co. KG)

Postdoctoral Fellow – Cardiovascular Stem Cell (Yale University, School of Medicine)

Postdoctoral Position (University of Rochester Medical Center)

Postdoctoral Position – Stem Cell Research (University of Washington)

Lecturer or Reader – Associate Professor (University of Reading)


Postdoctoral Fellow (Johns Hopkins School of Medicine)

Postdoctoral Fellow – Pluripotent Stem Cells (Faculty of Medicine, University of Ottawa)


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