ESC & iPSC News Volume 14.21 | Jun 5 2019

TOP STORY

Phosphorylation of Histone H3.3 at Serine 31 Promotes p300 Activity and Enhancer Acetylation

Researchers found that that H3.3-specific phosphorylation stimulated activity of the acetyltransferase p300 in trans, suggesting that H3.3 acted as a nucleosomal cofactor for p300. Depletion of H3.3 from mouse ESCs reduced acetylation on histone H3 at lysine 27 at enhancers. [Nat Genet] Abstract

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Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids

Using 11 different healthy and diseased pluripotent stem cell lines, investigators developed a reproducible method to derive multi-cellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells that exhibited transcriptomic resemblance to in vivo-derived tissues. [Cell Metab] Abstract | Graphical Abstract

Establishment of Porcine and Human Expanded Potential Stem Cells

Scientists report the derivation of porcine expanded (E)PSCs, which expressed key pluripotency genes, were genetically stable, permitted genome editing, differentiated to derivatives of the three germ layers in chimeras and produced primordial germ cell-like cells in vitro. Under similar conditions, human ESCs and iPSCs could be converted, or somatic cells directly reprogrammed, to EPSCs that displayed the molecular and functional attributes reminiscent of porcine EPSCs. [Nat Cell Biol] Abstract | Press Release

Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia by Inhibition of Ca²⁺/Calmodulin-Dependent Kinase II

Researchers developed AAV9-GFP-AIP, an adeno-associated viral vector in which a potent almodulin-dependent protein kinase II inhibitory peptide, was fused to GFP and expressed from a cardiomyocyte selective promoter. The vector was delivered systemically. Arrhythmia burden was evaluated using invasive electrophysiology testing in adult mice. [Circulation] Abstract

Exonuclease Requirements for Mammalian Ribosomal RNA Biogenesis and Surveillance

Using loss-of-function approaches in mouse ESCs and deep sequencing of ribosomal (r)RNA intermediates, the authors investigated the requirements of exonucleases known to be involved in 5.8S maturation at nucleotide resolution and explored the role of the Perlman syndrome–associated 3′–5′ exonuclease Dis3l2 in rRNA processing. [Nat Struct Mol Biol] Abstract

Derivation and Maintenance of Mouse Haploid Embryonic Stem Cells

The diploid status of most cells correlated with the number of probable alleles for each autosomal gene and made it difficult to target these genes via mutagenesis techniques. Investigators described a seven-week protocol for the derivation of mouse haploid ESCs from female gametes that also outlined how to maintain the cells once derived. [Nat Protoc] Abstract

Pax3 Cooperates with Ldb1 to Direct Local Chromosome Architecture during Myogenic Lineage Specification

Scientists report that activation of embryonic myogenesis was associated with establishment of long-range chromatin interactions centered on Pax3-bound loci. Using mass spectrometry and genomic studies, they identified the ubiquitously expressed LIM-domain binding protein 1 (Ldb1) as the mediator of looping interactions at a subset of Pax3 binding sites. [Nat Commun] Full Article | Press Release

Core Pluripotency Factors Promote Glycolysis of Human Embryonic Stem Cells by Activating GLUT1 Enhancer

To understand the mechanisms governing the metabolism of human (h)ESCs, the authors investigated the transcriptional regulation of glucose transporter 1 (GLUT1), a key glycolytic gene to maintain pluripotency. By combining the genome-wide data of binding sites of the core pluripotency factors, chromosomal interaction and histone modification in hESCs, they identified a potential enhancer of the GLUT1 gene in hESCs, denoted GLUT1 enhancer element. [Protein Cell] Abstract | Full Article

NeuroMesodermal Progenitors (NMPs): A Comparative Study between Pluripotent Stem Cells and Embryo Derived Populations

Investigators performed a single cell analysis of different in vitro NMP populations produced either from ESCs or epiblast stem cells and compared them to E8.25 CLE mouse embryos. In their analysis of this region their findings challenged the notion that NMPs could be defined by the exclusive coexpression of Sox2 and T at the mRNA level. [Development] Abstract

Feasibility of Repairing Full-Thickness Skin Defects by iPSC-Derived Epithelial Stem Cells Seeded on a Human Acellular Amniotic Membrane

Human urinary cells isolated from a healthy donor were reprogrammed into iPSCs and then induced into CD200⁺/ITGA6⁺ epithelial stem cells (EpSCs). Immunocytochemistry and RT-PCR were used to examine the characteristics of the induced EpSCs. iPSC-derived epithelial stem cells were cultured on a human acellular amniotic membrane, and cytocompatibility of the composite was analyzed by CCK8 assays and scanning electron microscopy. [Stem Cell Res Ther] Full Article

The Long Non-Coding RNA Snhg3 Is Essential for Mouse Embryonic Stem Cell Self-Renewal and Pluripotency

Researchers investigated the role of Small nucleolar RNA host gene 3 (Snhg3) in mouse ESCs (mESCs) through both loss-of-function and gain-of-function approaches. Alkaline phosphatase staining, secondary colony formation, propidium iodide staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to access self-renewal capacity, whereas immunofluorescence, qRT-PCR, and embryoid body formation were performed to examine pluripotency. [Stem Cell Res Ther] Full Article

Cell Cycle Dynamics of Mouse Embryonic Stem Cells in the Ground State and during Transition to Formative Pluripotency

By performing live imaging experiments of mouse ESCs (mESCs) bearing cell cycle reporters, investigators showed that cells in the pluripotent ground state displayed a cell cycle structure comparable to the reported for mESCs in serum-based media. Upon release from self-renewal, the cell cycle was rapidly accelerated by a reduction in the length of the G1 phase and of the S/G2/M phases, causing an increased proliferation rate. [Sci Rep] Full Article

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The Role of Ubiquitination in Regulating Embryonic Stem Cell Maintenance and Cancer Development

The authors provide an overview of ubiquitination machinery and discuss recent progress in ubiquitination-mediated regulation of embryonic stem cell maintenance and cancer biology. [Int J Mol Sci] Full Article

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Columbia University and Deerfield Management Launch Hudson Heights Innovations

Columbia University and Deerfield Management announced the creation of a major research and development alliance. The collaboration is intended to advance the translation of biomedical discoveries into transformative treatments for improved quality of life and cures for disease. [Columbia University] Press Release

The Trump Administration Will End Fetal Tissue Research by Government Scientists

Government scientists will no longer conduct research using fetal tissue, the Trump administration said, granting the wishes of anti-abortion groups and overruling the concerns of scientists. The Department of Health and Human Services said it has discontinued all internal research that involves fetal tissue, which is obtained through elective abortions. [STAT News] Editorial

Congress Weighs Dropping Ban on Altering the DNA of Human Embryos Used for Pregnancies

A congressional committee is expected to vote to drop a ban on altering the genomes of human embryos intended for pregnancies, which could open the door to creating babies with genetic material from three people or with genomes that have been modified in a way that would be inherited by their descendants, as China’s “CRISPR babies” were. [STAT News] Editorial

FDA Wins Major Victory in Campaign against Stem Cell Clinic

The US FDA won a major legal victory in its ongoing effort to crack down on clinics marketing bogus and potentially hazardous stem cell products. A federal judge in Miami granted the FDA an injunction to prevent the Florida-based US Stem Cell Clinic from offering treatments designed to create stem cells from body fat and administering them intravenously or directly into the spinal cords of patients to treat Parkinson’s disease, amyotrophic lateral sclerosis, chronic obstructive pulmonary disease and other serious conditions. [CNN] Editorial

Hungarians Protest against Proposed Government Takeover of Science

Thousands of scientists and their supporters marched through the streets of Budapest on 2 June to protest against a proposed law that would give the Hungarian government direct control of the country’s top research institutes. [Nature News] Editorial

NEW Biotech Week Boston
September 9-12, 2019
Boston, Massachusetts, United States

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NEW Postdoctoral Researcher – Cystic Fibrosis Stem Cell Models (The University of Alabama at Birmingham)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Dementia Treatment with iPSCs (Cardiff University)

Postdoctoral Associate – RNA Genomics in iPSCs (The Jackson Laboratory)

Postdoctoral Fellow – Stem Cells and Regenerative Medicine (German Research Center for Environmental Health)

Postdoctoral Associate – Stem Cell Differentiation in Immunology (University of Massachusetts Medical School)

Research Assistant – Stem Cells & Regenerative Medicine (Boston Children’s Hospital)

Postdoctoral Fellow – Pluripotent Stem Cells & Joint Tissue Development (Boston Children’s Hospital)

Postdoctoral Fellowship – Cell Fate and Cancer Initiation (University of Miami Miller School of Medicine)

Postdoctoral Fellow – Genetics and Epigenomics of iPSC Biology (Stanford University)

Assistant Associate Professor/Professor in Residence – Stem Cell Program (UC Davis)

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