ESC & iPSC News Volume 9.46 | Nov 26 2014

Multi-Kilobase Homozygous Targeted Gene Replacement in Human Induced Pluripotent Stem Cells
Scientists demonstrate efficient ‘knock-in’ targeted replacement of multi-kilobase genes in human induced pluripotent stem cells. Using a model system replacing endogenous human genes with their mouse counterpart, they performed a comprehensive study of targeting vector design parameters for homologous recombination. [Nucleic Acids Res] Full Article

The Dyskerin Ribonucleoprotein Complex as an OCT4/SOX2 Coactivator in Embryonic Stem Cells
Using a biochemically defined in vitro transcription system that mediates OCT4/SOX2 and coactivator-dependent transcription of the Nanog gene, researchers report the purification and identification of the dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator whose activity appears to be modulated by a subset of associated small nucleolar RNAs. [Elife] Abstract | Full Article

A Rare Human Syndrome Provides Genetic Evidence that WNT Signaling Is Required for Reprogramming of Fibroblasts to Induced Pluripotent Stem Cells
Researchers provide genetic evidence that WNT signaling is a requisite step during the induction of pluripotency. Fibroblasts from individuals with focal dermal hypoplasia, a rare genetic syndrome caused by mutations in the essential WNT processing enzyme PORCN, fail to reprogram with standard methods. [Cell Rep] Full Article | Graphical Abstract | Press Release

Efficient and Allele-Specific Genome Editing of Disease Loci in Human iPSCs
Scientists investigated the relative efficiencies of CRISPR/Cas9 and TALENs in human induced pluripotent stem cell (iPSC) lines for inducing both homologous donor-based precise genome editing and non-homologous end joining-mediated gene disruption. [Mol Ther] Abstract

Derivation and High Engraftment of Patient-Specific Cardiomyocyte-Sheet Using Induced Pluripotent Stem Cells Generated from Adult Cardiac Fibroblast
Scientists show that human cardiac induced pluripotent stem cells (hciPSCs) can be generated from cardiac fibroblasts and subsequently differentiated into exceptionally pure sheets of cardiomyocytes (CMs). The hciPSCs passed through all the normal stages of differentiation before assuming a CM identity. [Circ Heart Fail] Abstract

Stochastic Promoter Activation Affects Nanog Expression Variability in Mouse Embryonic Stem Cells
Nanog, a key transcription factor for pluripotency, displays heterogeneous expression in mouse embryonic stem cells, via mechanisms that are not fully understood. To understand this variability, researchers quantitatively analyzed Nanog transcription and found that Nanog was both infrequently transcribed, and transcribed in a pulsatile and stochastic manner. [Sci Rep] Full Article

Metabolic Profiling and Flux Analysis of MEL-2 Human Embryonic Stem Cells during Exponential Growth at Physiological and Atmospheric Oxygen Concentrations
Investigators undertook an in-depth characterization of MEL-2 human embryonic stem cells metabolic behavior during the exponential growth phase, combining metabolic profiling and flux analysis tools at physiological and atmospheric oxygen concentrations. [PLoS One] Full Article

Histone Deacetylase 1 and 3 Regulate the Mesodermal Lineage Commitment of Mouse Embryonic Stem Cells
Scientists found that trichostatin A, an inhibitor of histone deacetylase, could induce early differentiation of embryonic stem cells and promote mesodermal lineage differentiation. [PLoS One] Full Article

BMP-4 Increases Activin A Gene Expression during Osteogenic Differentiation of Mouse Embryonic Stem Cells
Scientists investigated the effect of bone morphogenetic protein (BMP)-4 on activin A gene expression during in vitro osteogenic differentiation of mouse embryonic stem cells. [Growth Factors] Abstract

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Mount Sinai Researchers Awarded Grant to Find New Stem Cell Therapies for Vision Recovery
The National Eye Institute, a division of the National Institutes of Health, has awarded researchers at the Icahn School of Medicine at Mount Sinai a five-year grant totaling $1 million that will support an effort to re-create a patients’ ocular stem cells and restore vision in those blinded by corneal disease. [The Mount Sinai Hospital (EurekAlert)] Press Release

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Proposed Rules Will Vastly Expand Trove of Clinical Trial Data Reported in U.S. Database
The amount of clinical data that drug companies must share with the public could soon vastly expand under a U.S. regulation proposed. Trial sponsors would need to report summary results for drugs and devices that are never approved – and not just for products that reach the market – under the proposal. [ScienceInsider] Editorial

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Postdoctoral Fellow – In Vitro Modeling of Human Skeletal Muscle Disease (Duke University)

Head of Cellular and Molecular Therapies Laboratory (NHS Blood & Transplant)

PhD Studentship – The Initial Network for Cellular Reprogramming to Pluripotency (University of Edinburgh)

Postdoctoral Position – Stem Cell and RNA Biology (Lund University)

Postdoctoral Position – Muscle Cell Therapy (I-Stem)

Postdoctoral Scientist – Stem Cell Biology (Texas Biomedical Research Institute)

Postdoctoral Fellow – Pluripotent Stem Cell Laboratory (University of California – San Diego)

Scientist – Reprogramming and Pluripotent Stem Cell Biology (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Human Pluripotent Stem Cell Biology (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

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