ESC & iPSC News Volume 10.16 | Apr 29 2015

Correction of Human Phospholamban R14del Mutation Associated with Cardiomyopathy Using Targeted Nucleases and Combination Therapy
Scientists generated induced pluripotent stem cells (iPSCs) from a patient harboring the PLN R14del mutation and differentiated them into cardiomyocytes (iPSC-CMs). They found that the PLN R14del mutation induced Ca²⁺ handling abnormalities, electrical instability, abnormal cytoplasmic distribution of PLN protein and increased expression of molecular markers of cardiac hypertrophy in iPSC-CMs. [Nat Commun] Full Article

A Regulatory Network Involving β-Catenin, E-Cadherin, PI3k/Akt, and Slug Balances Self-Renewal and Differentiation of Human Pluripotent Stem Cells In Response to Wnt Signaling
Scientists demonstrated that self-renewal versus differentiation of human embryonic stem cells in response to Wnt signaling was predominantly determined by a two-layer regulatory circuit involving β-catenin, E-cadherin, PI3K/Akt, and Slug in a time-dependent manner. [Stem Cells] Full Article

Identification of 2-[4-[(4-Methoxyphenyl)Methoxy]-Phenyl]Acetonitrile and Derivatives as Potent Oct3/4 Inducers
Using a cell-based high throughput screening campaign, the authors identified 2-[4-[(4-methoxyphenyl)methoxy]phenyl]acetonitrile (O4I1), enhanced Oct3/4 expression. Structural verification and modification by the chemical synthesis showed that O4I1 and its derivatives not only promoted expression and stabilization of Oct3/4, but also enhanced its transcriptional activity in diverse human somatic cells. [J Med Chem] Abstract

Non-Germline Restoration of Genomic Imprinting for a Small Subset of Imprinted Genes in Ubiquitin-Like PHD and RING Finger Domain-Containing 1 (Uhrf1) Null Mouse Embryonic Stem Cells
Investigators demonstrated that, although re-expression of UHRF1 in Uhrf1^-/- embryonic stem cells restored DNA methylation for the bulk genome but not for most of the imprinted genes, it did rescue DNA methylation for imprinted H19, Nnat and Dlk1 genes. [J Biol Chem] Abstract | Full Article

DNA Damage Response in Neonatal and Adult Stromal Cells Compared with Induced Pluripotent Stem Cells
Researchers determined the DNA damage response after radiation or treatment with N-methyl-N-nitrosurea (MNU) in induced pluripotent stem cells (iPSCs) compared with neonatal and bone marrow stromal cells. Neonatal and adult stromal cells showed no significant morphologically detectable cytotoxicity following treatment with 1 Gy or 1 mM MNU, whereas iPSCs revealed a much higher sensitivity. [Stem Cells Transl Med] Abstract

CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes
Investigators used tripronuclear zygotes to investigate clustered regularly interspaced short palindromic repeat-associated system (CRISPR/Cas9)-mediated gene editing in human cells. They found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene. [Protein Cell] Full Article

Nanotopographical Control of Human Embryonic Stem Cell Differentiation into Definitive Endoderm
Scientists developed a simple method to precisely fabricate electrospun poly(ε-caprolactone) fibers with four distinct average diameters at nano- and microscale levels. Human embryonic stem cells were cultured as clumps or single cells and induced into definitive endoderm differentiation to determine the optimal topography leading to the promoted differentiation compared with planar culture plates. [J Biomed Mater Res A] Abstract

The PRC2-Associated Factor C17orf96 Is a Novel CpG Island Regulator in Mouse ES Cells
Scientists found that the polycomb repressive complex 2 (PRC2)-associated protein C17orf96 was present at most CpG islands (CGIs) in mouse embryonic stem (ES) cells. At PRC2-rich CGIs, loss of C17orf96 resulted in an increased chromatin binding of Suz12 and elevated H3K27me3 levels concomitant with gene repression. [Cell Disc] Full Article

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Stem Cell Patent Announced
The United States Patent and Trademark Office issued a major patent to two scientists from UCLA. The patent covers a method used to identify human induced pluripotent stem cells in the lab using a tumor rejection antigen, which identifies stem cells that have reached a pluripotent state. [UCLA] Press Release

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Greek Government Raids Research Funds to Pay Public Salaries
Greek scientists are angry at what they see as a double-pronged government attack on the country’s research system: the confiscation of research funding to plug a hole in Greece’s ever worsening finances. [ScienceInsider] Editorial

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

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

Postdoctoral Fellow – Epithelial Stem Cells & Membrane Trafficking (New York University School of Medicine)

Postdoctoral Fellowship – Stem Cells & Epigenetics (National Institutes of Health)

Stem Cell Culture Scientist (Paramount Recruitment)

Postdoctoral Fellowship – Stem Cells & Epigenetics (National Institutes of Health)

PhD Position – Early Human Brain Development Modeling with hiPSCs (University of Bonn)

Postdoctoral Position – Induced Pluripotent Stem Cells to Study Metabolism and Gene Expression Regulating Neural Tube Development (Joslin Diabetes Center)

Postdoctoral Position – Human Induced Pluripotent Stem Cells (hiPSCs) and the Peripheral Nervous System (Inserm)

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