Volume 10.16 | Apr 29

ESC & iPSC News 10.16 April 29, 2015
ESC & iPSC News
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Erosion of X Chromosome Inactivation in Human Pluripotent Cells Initiates with XACT Coating and Depends on a Specific Heterochromatin Landscape
Scientists showed that, in human pluripotent stem cells (hPSCs), the inactive X chromosome has a specific heterochromatin landscape that predisposes it to erosion of X chromosome inactivation, a process that occurs spontaneously in hPSCs. [Cell Stem Cell] Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
The Histone Deacetylase SIRT6 Controls Embryonic Stem Cell Fate via TET-Mediated Production of 5-Hydroxymethylcytosine
Researchers demonstrated the interplay between the histone deacetylase sirtuin 6 (SIRT6) and the ten-eleven translocation enzymes (TETs). Embryonic stem cells derived from Sirt6 knockout mice were skewed towards neuroectoderm development. [Nat Cell Biol] Abstract

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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New Muscle for Old Hearts: Engineering Tissue from Pluripotent Stem Cells
Patient-derived induced pluripotent stem cells (iPSCs) are now available, which combine the advantages of autologous adult stem cells with the unlimited potential of embryonic stem cells for proliferation and differentiation. Intense research has driven forward recent dramatic progress in various areas of iPSC technology relevant for clinically applicable iPSC-based cellular therapies. [Hum Gene Ther] Abstract

Visit our reviews page to see a complete list of reviews in the ESC & iPSC research field.
BioTime’s Clinical Grade Stem Cells From Subsidiary ES Cell International to Be Used in Planned CIRM-Funded Preclinical Studies of Huntington’s Disease
BioTime, Inc. announced that the clinical-grade human embryonic stem (ES) cell lines from ES Cell International Pte Ltd will be used by University of California, Irvine scientists to continue promising research in the use of stem cells to treat Huntington’s disease under a $5 million grant from the California Institute for Regenerative Medicine. [BioTime, Inc.] Press Release

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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Canadian Budget Pushes Applied Research
The reigning Conservative party has introduced a budget that emphasizes applied research and scientific collaboration with industry. The Canada Foundation for Innovation would receive $1.33 billion in new money for university and hospital research facilities, to be doled out over six years beginning in 2017. [Nature News] Editorial

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
NEW Stem Cell Meeting on the Mesa
October 7-9, 2015
La Jolla, United States

NEW Cold Spring Harbor Stem Cell Biology Meeting
October 7-11, 2015
Cold Spring Harbor, United States

Visit our events page to see a complete list of events in the ESC & iPSC community.
NEW Postdoctoral Position – Stem Cell Biology, Epigenetics & Cancer (Albert Einstein College of Medicine of Yeshiva University)

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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