ESC & iPSC News Volume 13.24 | Jun 20 2018

TOP STORY

Prospectively Isolated Tetraspanin⁺ Neoblasts Are Adult Pluripotent Stem Cells Underlying Planaria Regeneration

Scientists unveiled a novel subtype of neoblast characterized by high levels of PIWI-1 mRNA and protein and marked by a conserved cell-surface protein-coding gene, tetraspanin 1 (tspan-1). tspan-1-positive cells survived sub-lethal irradiation, underwent clonal expansion to repopulate whole animals, and when purified with an anti-TSPAN-1 antibody, rescued the viability of lethally irradiated animals after single-cell transplantation. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Esrrb Unlocks Silenced Enhancers for Reprogramming to Naive Pluripotency

The authors showed that the orphan nuclear receptor Esrrb played a pioneering role in recruiting the core pluripotency factors Oct4, Sox2, and Nanog to inactive enhancers in closed chromatin during the reprogramming of epiblast stem cells. Esrrb bound to silenced enhancers containing stable nucleosomes and hypermethylated DNA, which are inaccessible to the core factors. [Cell Stem Cell] Abstract | Graphical Abstract

Determining the Pathogenicity of a Genomic Variant of Uncertain Significance Using CRISPR/Cas9 and Human-Induced Pluripotent Stem Cells

Assessment of the pathogenic nature of a genome-edited isogenic line carrying a known pathogenic MYL3 mutation, MYL3_(170C>G), and a carrier-specific iPSC-derived cardiomyocyte line, carrying a MYBPC3_(961G>A) hypertrophic cardiomyopathy variant, demonstrated the ability of this combined platform to provide both pathogenic and benign assessments. [Circulation] Abstract | Press Release

Asf1a Resolves Bivalent Chromatin Domains for the Induction of Lineage-Specific Genes during Mouse Embryonic Stem Cell Differentiation

Investigators showed that Asf1a, a histone chaperone involved in nucleosome assembly and disassembly, regulated the resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation. Deletion of Asf1a did not affect the silencing of pluripotent genes, but compromised the expression of lineage-specific genes during ES cell differentiation. [Proc Natl Acad Sci USA] Abstract

Random Mutagenesis, Clonal Events, and Embryonic or Somatic Origin Determine the mtDNA Variant Type and Load in Human Pluripotent Stem Cells

Early-passage human ESCs (hESCs) carried few and low-load heteroplasmic variants, similar to those identified in oocytes and inner cell masses. The number and heteroplasmic loads of these variants increased with prolonged cell culture. Scientists found that early-passage human iPSCs carry much higher loads of mtDNA variants than hESCs, which single-fibroblast sequencing proved pre-existed in the source cells. [Stem Cell Reports] Full Article | Graphical Abstract

DSG2 Is a Functional Cell Surface Marker for Identification and Isolation of Human Pluripotent Stem Cells

The authors raised a monoclonal antibody and identified its target antigen as desmoglein-2 (DSG2). DSG2 co-localized with human PSC (hPSC)-specific cell surface markers, and its expression was rapidly downregulated upon differentiation. The depletion of DSG2 markedly decreased hPSC proliferation and pluripotency marker expression. [Stem Cell Reports] Full Article

Atorvastatin Inhibits the HIF1α-PPAR Axis, Which Is Essential for Maintaining the Function of Human Induced Pluripotent Stem Cells

The administration of atorvastatin to human iPSCs (hiPSCs) caused the expression of hypoxia inducible factor (HIF)1α mRNA to be unchanged at 6 hr and downregulated at 24 hr. Inhibition of the survival of hiPSCs was confirmed by HIF1α-peroxisome proliferator-activated receptor (PPAR) axis inhibition. [Mol Ther] Full Article | Graphical Abstract

Silver Nanoparticles Inhibit Neural Induction in Human Induced Pluripotent Stem Cells

Researchers observed that exposure to silver nanoparticles (AgNPs) reduced the expression of several neural differentiation marker genes, including OTX2, an early biomarker for neurogenesis in iPSCs. They observed that AgNPs decreased intracellular ATP levels in iPSCs and revealed that AgNPs induced mitochondrial fragmentation and reduced the level of mitochondrial fusion protein mitofusin 1. [Nanotoxicology] Abstract

miR-7 Modulates Human Embryonic Stem Cell Differentiation into Insulin-Producing Beta-Like Cells and Contributes to Cell Maturation

Investigators found that miR-7 is differentially expressed during the differentiation of human ESCs into a beta cell-like phenotype and that its modulation plays an important role in generating mature pancreatic beta cells. [Mol Ther Nucleic Acids] Abstract | Full Article

Clonal Dynamics Studied in Cultured Induced Pluripotent Stem Cells Reveal Major Growth Imbalances within a Few Weeks

Scientists assessed potential reduction of clonal diversity by inherent growth imbalances. In three human iPS cell lines as well as primary human fibroblasts and two widely used human cell lines as controls, they observed a marked reduction in sub-clonal diversity over time of culture (weeks). After 38 passages, all iPS cultures consisted of less than ten residual clones. [Stem Cell Res Ther] Full Article

Microphysiological Systems Meet hiPSC Technology – New Tools for Disease Modeling of Liver Infections in Basic Research and Drug Development

Human iPSCs (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). Investigators summarize current protocols of HLC generation and highlight recently established microphysiological models suitable to resemble physiological hepatocyte function in vitro. [Adv Drug Deliv Rev] Full Article | Graphical Abstract

Instructions for Assembling the Early Mammalian Embryo

The authors review the instructions revealed thus far, and then discuss remaining challenges to discover upstream factors controlling cell fate determination, test the role of mechanisms based on biological noise, and take advantage of recent technological developments to advance the spatial and temporal resolution of our current understanding. [Dev Cell] Abstract

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

The Scripps Research Institute and ShangPharma Innovation Announce Translational Research Collaboration

The Scripps Research Institute (TSRI) and ShangPharma Innovation, Inc. announced a strategic collaboration to accelerate the development of innovative drug candidates through scientific collaboration, a services relationship with Shanghai ChemPartner Co. Ltd., and sponsored research at TSRI and its drug discovery affiliate, California Institute for Biomedical Research. [The Scripps Research Institute] Press Release

U.K. Creates £2.5B Investment Program to Help Startups Grow

The U.K. has set up a £2.5 billion ($3.6 billion) patient capital program. The fund is part of an initiative to help British biotechs grow into standalone midsized businesses, rather than sell up at the first sign of a takeover bid from overseas. [Fierce Biotech] Press Release

U.S. Legislators Back Larger Facilities Budget for NSF

The National Science Foundation (NSF) in Alexandria, Virginia, is in line for a budget increase of 4% to 5% next year. That assessment is based on bills approved recently by the spending committees in both chambers of Congress. Lawmakers have also signaled support for growing the account that NSF uses to build major new scientific facilities. [ScienceInsider] Editorial

Why the Medical Research Grant System Could Be Costing Us Great Ideas

The medical research grant system in the United States, run through the National Institutes of Health, is intended to fund work that spurs innovation and fosters research careers. In many ways, it may be failing. [The New York Times] Editorial

House Bill Gives NIH a 3% Boost in 2019, to $38.3 Billion

A draft bill released by a House of Representatives spending panel would give the National Institutes of Health (NIH) in Bethesda, Maryland, a $1.25 billion raise in 2019, to $38.3 billion. That is 3% more than this year’s level and $4.1 billion more than President Donald Trump’s administration had requested. [ScienceInsider] Editorial

Hundreds of U.S. Scientists Urge More Transparency in Animal Research

Breaking with a history of reticence, nearly 600 scientists, students, and lab animal workers published a letter in USA Today this morning that calls on U.S. research institutions to “embrace openness” about their animal research. [ScienceInsider] Editorial

NEW The New York Stem Cell Foundation (NYSCF) Conference
October 23-24, 2018
New York, New York, United States

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

NEW Postdoctoral Training Fellow – Vertebrate Neural Tube Development (The Francis Crick Institute)

NEW Postdoctoral Positions – Human Functional Genomics of Aging & Disease (Albert Einstein College of Medicine of Yeshiva University)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Associate/PhD Position – iPSCs & Neurodegenerative Disease (TU Dresden)

Research Specialist – Cardiovascular Disease (University of Illinois)

Postdoctoral Position – Human Pluripotent Stem Cell-Based Cell Therapy in Type 1 Diabetes (The Novo Nordisk Foundation Center for Stem Cell Biology – DanStem)

Postdoctoral Research Associate – Embryonic Stem Cell Research (University of Illinois)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University Feinberg School of Medicine)

Senior Scientist/ Scientist – Tissue Engineering (Novoheart)

Postdoctoral Fellow – hiPSC Based Cardiac Regeneration (Duke University)

Postdoctoral Fellow – Human Skeletal Muscle Disease Modeling and Regeneration (Duke University)

PhD Candidate Position – Cardiovascular Diseases and iPSCs (University Medical Center Göttingen)

Scientist/Senior Scientist – Bioprocess Engineering (Bluerock Therapeutics, LLC.)

Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Postdoctoral Fellow – Stem Cells, Development and Cancer (Albert Einstein College of Medicine)

Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University)

Postdoctoral Fellow – Stem Cell Biology (City of Hope)

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