ESC & iPSC News Volume 14.18 | May 15 2019

TOP STORY

Proneural Factors Ascl1 and Neurog2 Contribute to Neuronal Subtype Identities by Establishing Distinct Chromatin Landscapes

Using direct neuronal programming of embryonic stem cells, researchers found that two main vertebrate proneural factors, Ascl1 and neurogenin 2 (Neurog2), induced different neuronal fates by binding to largely different sets of genomic sites. Their divergent binding patterns were not determined by the previous chromatin state, but were distinguished by enrichment of specific E-box sequences that reflected the binding preferences of the DNA-binding domains. [Nat Neurosci] Abstract

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SALL3 Expression Balance Underlies Lineage Biases in Human Induced Pluripotent Stem Cell Differentiation

For efficient selection of human iPSC (hiPSC) lines suitable for differentiation into desired cell lineages, the authors identified SALL3 as a marker to predict differentiation propensity. SALL3 expression in hiPSCs correlated positively with ectoderm differentiation capacity and negatively with mesoderm/endoderm differentiation capacity. [Nat Commun] Full Article

Generation, Transcriptome Profiling, and Functional Validation of Cone-Rich Human Retinal Organoids

Scientists report the generation, transcriptome profiling, and functional validation of cone-rich human retinal organoids differentiated from human ESCs (hESCs) using an improved retinal differentiation system. Induced by extracellular matrix, aggregates of hESCs formed single-lumen cysts composed of epithelial cells with anterior neuroectodermal/ectodermal fates, including retinal cell fate. [Proc Natl Acad Sci USA] Abstract

Multi-Omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency

Investigators dissected the dynamics of pluripotent state transitions underlying pre- to post-implantation epiblast differentiation. Through comprehensive mapping of the proteome, phosphoproteome, transcriptome, and epigenome of embryonic stem cells transitioning from naive to primed pluripotency, they found that rapid, acute, and widespread changes to the phosphoproteome preceded ordered changes to the epigenome, transcriptome, and proteome. [Cell Syst] Full Article | Graphical Abstract

WNT/NOTCH Pathway Is Essential for the Maintenance and Expansion of Human MGE Progenitors

The authors report that WNT/CTNNB1 signaling played an essential role in maintaining medial ganglionic eminence (MGE)-like cells derived from human PSCs. Ablation of CTNNB1 in MGE cells led to precocious cell-cycle exit and advanced neuronal differentiation. Activation of WNT signaling through genetic or chemical approach was sufficient to maintain medial ganglionic eminence cells in an expandable manner with authentic neuronal differentiation potencies through activation of endogenous NOTCH signaling. [Stem Cell Reports] Full Article | Graphical Abstract

De Novo DNA Methylation at Imprinted Loci During Reprogramming into Naive and Primed Pluripotency

Scientists conducted a comprehensive analysis of CpG island (CGI) methylation during somatic cell reprogramming. Although most CGIs remained hypomethylated, a small subset of CGIs, particularly at several imprinting control regions (ICRs), were often de novo methylated in reprogrammed PSCs. Such de novo ICR methylation was linked with the silencing of reprogramming factors, which occurred at a late stage of reprogramming. [Stem Cell Reports] Full Article | Graphical Abstract

CRISPR/Cas9-Mediated Generation of a Tyrosine Hydroxylase Reporter iPSC Line for Live Imaging and Isolation of Dopaminergic Neurons

Researchers used CRISPR/Cas9-based editing to generate a human iPSC line expressing a fluorescent protein (mOrange) knocked-in at the last exon of the TH locus. After differentiation of the TH-mOrange reporter iPSC line, they confirmed that mOrange expression faithfully mimicked endogenous TH expression in iPSC-derived dopaminergic neurons. [Sci Rep] Full Article

Non-Invasive Detection of DNA Methylation States in Carcinoma and Pluripotent Stem Cells Ssing Raman Microspectroscopy and Imaging

To investigate global DNA methylation changes, human colon carcinoma HCT116 cells, which were hypomorphic for DNA methyltransferase 1, therefore showing a lower global DNA methylation, were compared to HCT116 wildtype cells. As a model system for early embryogenesis, murine embryonic stem cells were adapted to serum-free 2i medium, leading to a significant decrease in DNA methylation. [Sci Rep] Full Article

Effect of Embryo Cryopreservation on Derivation Efficiency, Pluripotency, and Differentiation Capacity of Mouse Embryonic Stem Cells

Assessments of isolated mouse ESC lines included simple karyotype analysis; polymerase chain reaction of the testis-determining gene; determination of alkaline phosphatase activity; expressions of pluripotent transcription factors Oct4, Rex1, Sox2, and Nanog by reverse transcription polymerase chain reaction; and immunocytochemistry assessment of OCT4 and SSEA-I expressions at the protein level. [J Cell Physiol] Abstract

Incorporated-bFGF Polycaprolactone/Polyvinylidene Fluoride Nanocomposite Scaffold Promotes Human Induced Pluripotent Stem Cells Osteogenic Differentiation

Embedded basic fibroblast growth factor (bFGF)-polycaprolactone-polyvinylidene fluoride (PCL-PVDF) hybrid was designed and fabricated by electrospinning as a bio-functional nanofibrous scaffold for bone tissue engineering. After morphological characterization of the PCL-PVDF (bFGF) scaffold, nanofibers biocompatibility was investigated by culturing of the human iPSCs. [J Cell Biochem] Abstract

Derivation of Mimetic γδ T Cells Endowed with Cancer Recognition Receptors from Reprogrammed γδ T Cell

Scientists reprogrammed γδ T cell into iPSCs (γδ T-iPSCs) to circumvent the risk of graft-versus-host disease. To target multiple cancer-associated antigens, they used an natural killer cell-promoting protocol to differentiate γδ T-iPSCs and to induce expression of natural killer receptors. [PLoS One] Full Article

Development of Human In Vitro Brain-Blood Barrier Model from Induced Pluripotent Stem Cell-Derived Endothelial Cells to Predict the In Vivo Permeability of Drugs

The authors generated a human in vitro brain-blood barrier (BBB) model by differentiating the human iPSC (hiPSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins and endothelial markers, as well as high trans-endothelial electrical resistance and γ-GTPase activity. [Neurosci Bull] Abstract

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Engineering Tissues from Induced Pluripotent Stem Cells

The authors summarize impressive examples of burgeoning research by leading groups that harness cellular and tissue engineering principles to study mechanisms of disease and injury, and in the context of repairing damaged tissue. These studies highlight both the power of these approaches, as well as ongoing challenges in the field. [Tissue Eng Part A] Abstract

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

Novo Nordisk Increases Commitment to Stem Cell-Based Therapies

Novo Nordisk announced an increased commitment to stem cell-based therapies and an expansion of the focus on type 1 diabetes into other serious chronic diseases. This has been made possible through an exclusive collaboration with the University of California San Francisco in which a first milestone in the development of human embryonic stem cell lines has been reached. [Novo Nordisk A/S] Press Release

Awards to Accelerate Translation of 3Rs Technologies for Industrial Use

Four grants totaling £200,000 have been awarded under the new Technologies to Tools scheme, launched as a strategic collaboration with Medicines Discovery Catapult. The awards will support the translation of technologies developed through the National Centre for the Replacement Refinement & Reducation of Animals in Research grant funding into industry-ready products and services, to support improved medicines discovery and maximise the 3Rs impacts. [The National Centre for the Replacement Refinement & Reducation of Animals in Research] Press Release

German Ethics Council Expresses Openness to Eventual Embryo Editing

A panel of government-appointed experts in Germany agreed unanimously that the human germline — DNA that is inherited by children from their parents — “is not inviolable,” rejecting one objection to using genome editing technologies such as CRISPR to make heritable changes in the DNA of human embryos, sperm, or eggs. [STAT] Editorial

Singapore Passes ‘Fake News’ Law Following Researcher Outcry

Singapore’s parliament has passed a law that bans the spreading of “a false statement of fact” that harms the public interest. Researchers and human-rights groups opposed the regulation, and warn that it will stifle academic debate. The Protection from Online Falsehoods and Manipulation Bill, which passed last week, authorizes Singapore’s ministers to order social media and messaging platforms to remove the material deemed false by authorities, or force them to run corrections. [Nature News] Editorial

Europe Abandons Plans for ‘Flagship’ Billion-Euro Research Projects

A consortium, called LifeTime, aims to use three emerging technologies—machine learning, the study of single cells, and lab-grown organlike tissues called organoids—to map how human cells change over time and develop diseases. It is one of six candidates in the latest round of ambitious proposals for European flagships, billion-euro research projects intended to run for 10 years. There is just one snag: The European Commission has decided that it won’t launch any of them. [ScienceInsider] Editorial

Europe’s Premier Research Funder Appoints New President

Nanobiologist Mauro Ferrari will become president of the European Research Council, the European Union’s premier funder of basic research. Ferrari’s appointment comes as the agency faces challenges to its budget, which cannot currently cover all of the grants that evaluators deem fundable. [Nature News] Editorial

NEW Cell & Gene Meeting on the Mesa
October 2-4, 2019
Carlsbad, California, United States

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

NEW Postdoctoral Lecturer – iPSCs in Neuronal Modeling (Great Ormond Street Institute of Child Health)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

Postdoctoral Fellow – iPSC Based Disease Modelling (The New York Stem Cell Foundation)

Lab Manager – Chromatin’s Role in Pluripotency & Self-Renewal (Howard Hughes Medical Institute)

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 – iPSCs and Differentiated Neurons (Howard Hughes Medical Institute)

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

Postdoctoral Position – Human Pluripotent Stem Cell Biology (Washington University School of Medicine)

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

Staff Scientist – Transcriptional Control in Development and Disease (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow Positions – Human iPSCs, Epigenetics, Hematopoietic Stem Cell Biology, and Blood Cancers (Nationwide Children’s Hospital & Ohio State University)

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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