ESC & iPSC News Volume 14.05 | Feb 13 2019

TOP STORY

Folliculin Regulates mTORC1/2 and WNT Pathways in Early Human Pluripotency

Researchers showed that folliculin (FLCN) knock-out (KO) human ESCs (hESCs) maintained the naïve pluripotent state but could not exit the state since the critical transcription factor TFE3 remained active in the nucleus. Treatment of FLCN KO hESC with a Wnt inhibitor, but not ESRRB/FLCN double mutant, rescued the cells, allowing the exit from the naïve state. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

Generation of Pulmonary Neuroendocrine Cells and SCLC-Like Tumors from Human Embryonic Stem Cells

The authors demonstrated that inhibition of NOTCH signaling induced up to 10% of lung progenitor cells to form pulmonary neuroendocrine cells (PNECs), putative precursors to small cell lung cancers (SCLCs), and they could increase PNECs by reducing levels of retinoblastoma proteins with inhibitory RNA. [J Exp Med] Abstract

CNTN5^-/+ or EHMT2^-/+ human iPSC-Derived Neurons from Individuals with Autism Develop Hyperactive Neuronal Networks

Scientists developed a set of procedures to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with autism spectrum disorder. [eLife] Full Article | Press Release

Species-Specific Maturation Profiles of Human, Chimpanzee and Bonobo Neural Cells

Researchers utilized iPSC technology to investigate the development of cortical pyramidal neurons following migration and maturation of cells grafted in the developing mouse cortex. They showed differential migration patterns in human neural progenitor cells compared to those of chimpanzees and bonobos both in vitro and in vivo, suggesting heterochronic changes in human neurons. [eLife] Full Article

The Induction of Core Pluripotency Master Regulators in Cancers Defines Poor Clinical Outcomes and Treatment Resistance

Core pluripotency stem cell master regulators along with epithelial-mesenchymal transition markers were induced in human prostate, breast, lung, bladder, colorectal, and renal cancer cells. With a focus on prostate cancer, the culture-based induction of core pluripotent stem cell regulators was shown to promote survival in castrate conditions-mimicking first line treatment resistance with hormonal therapies. [Oncogene] Full Article

Generation of Induced Pluripotent Stem Cells Using Elastin Like Polypeptides as a Non-Viral Gene Delivery System

Results of the gel retardation assay demonstrated efficient complexation of elastin-like polypeptides with a plasmid containing the four Yamanaka stem cell factors, Oct-4, Klf4, c-myc, and Sox2. After transfection, the iPSCs showed embryonic stem cell-like characteristics, including expression of endogenous pluripotency genes, differentiation into three germ layer lineages, and formation of teratomas in vivo. [BBA-Mol Basis Dis] Abstract

Autonomous Trisomic Rescue of Down Syndrome Cells

Scientists continuously cultivated iPSCs with chromosome 21 trisomy for more than 70 weeks, and serendipitously obtained revertant cells with normal chromosome 21 diploids from the trisomic cells during long-term cultivation. Repeated experiments revealed that this trisomy rescue was not due to mosaicism of chromosome 21 diploid cells and occurred at an extremely high frequency. [Lab Invest] Full Article

Live-Cell Imaging of Subcellular Structures for Quantitative Evaluation of Pluripotent Stem Cells

The phase distribution (PD) image and its derived PD index reflected mitochondrial content, enabling quantitative evaluation of the degrees of somatic cell reprogramming and PSC differentiation. Moreover, the PD index allowed unbiased grouping of PSC colonies into those with high or low pluripotency without the aid of invasive methods. [Sci Rep] Full Article

DRUGPATH – A Novel Bioinformatic Approach Identifies DNA-Damage Pathway as a Regulator of Size Maintenance in Human ESCs and iPSCs

Researchers showed that human amniotic fluid stem cells utilized distinct interactomes compared to human (h) ESCs/hiPSCs and that pathways orchestrating cell cycle and apoptosis were strongly interconnected, while pathways regulating survival and size were not. Interestingly, hESCs/hiPSCs regulated their size by growing exact additional sizes during each cell cycle. [Sci Rep] Full Article

Ethanol Promotes Differentiation of Embryonic Stem Cells through Retinoic Acid Receptor-γ

Using reporter assays, ChIP assays, and retinoic acid receptor-γ (RARγ)-knockout ESC lines generated by CRISPR/Cas9 or homologous recombination, scientists demonstrated that ethanol signaled via RARγ binding to all-trans-retinoic acid response elements in differentiation-associated gene promoters or enhancers. [J Biol Chem] Abstract | Full Article

An Improved Method for Differentiating Mouse Embryonic Stem Cells into Cerebellar Purkinje Neurons

Using a recently described neural differentiation media, investigators generated monolayers of neural progenitor cells from mouse ESCs and differentiated them into Purkinje neuron (PN) precursors using specific extrinsic factors. These PN precursors were then differentiated into mature PNs by co-culturing them with granule neuron precursors also derived from neural progenitors using different extrinsic factors. [Cerebellum] Abstract

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Induced Pluripotent Stem Cells in Disease Modeling and Drug Discovery

Organoids and human-rodent chimeras more accurately mirror the diverse cellular ecosystems of complex tissues and are being applied to iPSC disease models to recapitulate the pathobiology of a broad spectrum of human maladies, including infectious diseases, genetic disorders and cancer. [Nat Rev Genet] Abstract

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

Cellect Begins Collaboration with Washington University in Preparation for First US Clinical Trial Using Cellect’s ApoGraft™ for Bone Marrow Transplantations

This will be the first clinical trial in the US using the company’s ApoGraft stem cell selection technology, which is designed to prevent acute graft-versus-host disease following bone marrow transplantation. [Cellect Biotechnology Ltd. (PR Newswire Association LLC.)] Press Release

Fate Therapeutics Announces FDA Clearance of IND Application for World’s First Cell Therapy Derived from an Engineered Pluripotent Stem Cell

Fate Therapeutics, Inc. announced that the FDA has allowed its Investigational New Drug (IND) application for FT516, the company’s off-the-shelf natural killer cell product candidate derived from a clonal master iPSC line engineered to express a novel CD16 Fc receptor. [Fate Therapeutics, Inc.] Press Release

New Cell-Based Technology by Cytonus Aims to Revolutionize the Fight against Cancer and Inflammatory Diseases

Cytonus Therapeutics Inc. announced that it has developed Cargocytes^™, a first-of-its-kind, controllable, cell-based platform technology for delivery of biologics. Cargocytes are engineered allogenic cell lines that can carry a variety of payloads like small molecule compounds, gene editing therapies, therapeutic RNAs, and powerful biologics such as immune modulating cytokines, antibodies and oncolytic viruses. [Cytonus Therapeutics Inc. (Business Wire, Inc.)] Press Release

UC Berkeley Team to Be Awarded CRISPR Patent

The University of California (UC), Berkeley, and its partners in developing CRISPR gene editing will receive the patent at the heart of an intellectual property dispute between the Berkeley team and the Broad Institute and its CRISPR collaborators. [The Scientist] Editorial

Restructure Spurs Protest at Indonesia’s Largest Research Institution

Hundreds of scientists in Indonesia protested against a major reorganization of the country’s largest research institution that is set to relocate more than 1,400 science-support jobs. The head of the Indonesian Institute of Sciences (LIPI), Laksana Tri Handoko, says the changes will make the organization more efficient and will allow scientists to concentrate on research, which will help to transform LIPI into a world-class research institute. [Nature News] Editorial

NEW 3^rd SUNRiSE Meeting : New Advances in Cancer Stem Cells
May 16-17, 2019
Nice, France

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

NEW Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

NEW Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

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

Scientist – Cell Culture Media and Cell Line Development (STEMCELL Technologies Inc.)

PhD Position – Stem Cell Research (Luxembourg Institute of Health)

Postdoctoral Position – Stem Cell Science and Genome Editing (Max Delbrück Center For Molecular Medicine)

Postdoctoral Research Fellow – Discovery Oncology (Merck)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

Postdoctoral Fellow – Stem Cell Biology (City of Hope)

Senior Laboratory Research Scientist – Pluripotent Stem Cell Research (The Francis Crick Institute)

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

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

Postdoctoral Positions – PSC-Derived Human Lung Organoids (Columbia University Irving Medical Center)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (UC Davis)

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