ESC & iPSC News Volume 14.27 | Jul 17 2019

TOP STORY

Generation of Quiescent Cardiac Fibroblasts from Human Induced Pluripotent Stem Cells for In Vitro Modeling of Cardiac Fibrosis

Scientists developed a robust chemically-defined protocol that generated cardiac fibroblasts (CFs) from human iPSCs. Functional studies confirmed that iPSC-derived CFs preserved a quiescent phenotype and highly resembled primary CFs at the transcriptional, cellular, and functional levels. They demonstrated that this cell-based platform was sensitive to both pro- and anti-fibrosis drugs. [Circ Res] Abstract

(Ranked by impact factor of the journal)

Generation of Expandable Human Pluripotent Stem Cell-Derived Hepatocyte-Like Liver Organoids

The authors developed a novel method to efficiently and reproducibly generate functionally mature human hepatic organoids derived from PSCs, including human ESCs and induced PSCs. The maturity of the organoids was validated by a detailed transcriptome analysis and functional performance assays. [J Hepatol] Abstract | Graphical Abstract

NF-Y Controls Fidelity of Transcription Initiation at Gene Promoters through Maintenance of the Nucleosome-Depleted Region

Researchers showed that the histone-fold domain protein NF-Y, a ubiquitously expressed transcription factor, controlled the fidelity of transcription initiation at gene promoters in mouse ESCs. They report that NF-Y maintained the region upstream of transcription start sites in a nucleosome-depleted state while simultaneously protecting this accessible region against aberrant and/or ectopic transcription initiation. [Nat Commun] Full Article

Systematic Allelic Analysis Defines the Interplay of Key Pathways in X Chromosome Inactivation

Investigators describe a systematic analysis of Xist-mediated allelic silencing in mouse ESC-based models. they go on to show that Spen, recruited through the Xist A-repeat, played a central role, being critical for silencing of all except a subset of weakly expressed genes. [Nat Commun] Full Article

The RNA Exosome Nuclease Complex Regulates Human Embryonic Stem Cell Differentiation

Scientists report that the surveillance pathway mediated by the RNA exosome nuclease complex repressed ESC differentiation. Depletion of the exosome expedited differentiation of human ESCs into all three germ layers. LINE-1 retrotransposons and specific miRNAs, lncRNAs, and mRNAs that encode developmental regulators or affect their expression were all bound by the exosome and increased in level upon exosome depletion. [J Cell Biol] Abstract

Gaining Insights into the Function of Post-Translational Protein Modification Using Genome Engineering and Molecular Cell Biology

The authors combined molecular and cellular biology with CRISPR/Cas9 mediated genome engineering to pinpoint the function of serine 12 (S12) of OCT4 in ESCs. Generation of isogenic mouse ESCs that endogenously ablate S12 revealed no effects on pluripotency and self-renewal, potentially due to compensation by other phosphorylation events. [J Mol Biol] Abstract

REV-ERBα and REV-ERBβ Function as Key Factors Regulating Mammalian Circadian Output

Researchers established a Rev–erbα/Rev–erbβ double-knockout mouse ESC model and analyzed the circadian clock and clock-controlled output gene expressions. They revealed that the double knockout of both Rev–erbα and Rev–erbβ did not abrogate expression rhythms of E-box-regulated core clock genes but drastically changed a diverse set of other rhythmically-expressed output genes. [Sci Rep] Full Article

Analysis of the 4q35 Chromatin Organization Reveals Distinct Long-Range Interactions in Patients Affected with Facio-Scapulo-Humeral Dystrophy

Using iPSC, investigators examined whether chromatin organization was inherited after reprogramming or acquired during differentiation and showed that folding of the 4q35 region was modified upon differentiation. [Sci Rep] Full Article

Presynaptic Dysfunction in Neurons Derived from Tay-Sachs iPSCs

Scientists generated iPSCs derived from patients with Tay-Sachs disease (TSD), and found similar potential for neural differentiation between TSD-iPSCs and normal iPSCs, although neural progenitor cells derived from the TSD-iPSCs exhibited enlarged lysosomes and upregulation of the lysosomal marker, LAMP1, caused by the accumulation of GM2 ganglioside. [Neuroscience] Abstract | Graphical Abstract

Subscribe to one of our other 19 science newsletters such as Cell Therapy News & Mesenchymal Cell News.

Liver Organoids: From Basic Research to Therapeutic Applications

Liver organoids have now been established for multiple species from induced pluripotent stem cells, embryonic stem cells, hepatoblasts and adult tissue-derived cells. These represent a promising addition to our toolbox to gain a deeper understanding of this complex organ. [Gut] Abstract

Single-Cell Multimodal Transcriptomics to Study Neuronal Diversity in Human Stem Cell-Derived Brain Tissue and Organoid Models

The authors discuss how the emergence of new single-cell genomics methods may help benchmark and optimize the tissue engineering process. The inherent heterogeneity and variability of reprogrammed brain tissue may conceal important disease mechanisms if not accounted for by rigorous experimental design. [J Neurosci Methods] Abstract | Graphical Abstract

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

Fujifilm and Axcelead Drug Discovery Partners Begin Collaborating to Advance Drug Discovery Solutions Using iPSCs

FUJIFILM Corporation and Axcelead Drug Discovery Partners Inc. announced a collaboration to provide customers with a human iPSC-based integrated platform for drug discovery solutions. Through the collaborations, Fujifilm and Axcelead aim to cater new approaches using iPSC to accelerate drug discovery of clients. [FUJIFILM Holdings America Corporation] Press Release

Epistem Licence Hubrecht Organoid Technology to Expand Preclinical Toxicology Service Portfolio

Epistem Limited announced the expansion of its in vitro model portfolio by the completion of an agreement with Hubrecht Organoid Technology to enable the delivery of an increased range of multi species organoid models. Services are focused on the identification of off target or off tissue intestinal toxicities associated with various therapeutics. [Epistem Ltd.] Press Release

The Plan to Mine the World’s Research Papers

Carl Malamud is on a crusade to liberate information locked up behind paywalls — and his campaigns have scored many victories. Now, the 60-year-old American technologist is turning his sights on a new objective: freeing paywalled scientific literature. And he thinks he has a legal way to do it. [Nature News] Editorial

US Senators Call for International Guidelines for Germline Editing

Senators Dianne Feinstein, Marco Rubio, and Jack Reed introduced a resolution calling for global collaboration in developing guidelines for the use of gene editing technologies in the context of reproduction. [The Scientist] Editorial

NEW Cell Symposia: Gene and Cell Based Therapies: CRISPR, Stem Cells & Beyond
March 2-4, 2020
San Francisco, California, United States

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

NEW Tenure-Track Faculty Position – Stem Cell Biology & Regenerative Medicine (Icahn School of Medicine at Mount Sinai)

Research Technologist – Pluripotent Stem Cell Biology (STEMCELL Technologies Inc.)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

Research Technician – Beta Cell Production from Human PSCs (Helmholtz Zentrum München)

Senior Scientist – Cell Engineering and Characterization (Merck & Co., Inc)

Associate Professor – Developmental and Stem Cell Biology (The University of Hong Kong)

Postdoctoral Fellows – Striated Muscle Regeneration (Duke University)

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

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

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

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

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in ESC & iPSC News? Click here to submit!

Comments or suggestions? Submit your feedback here.