ESC & iPSC News Volume 12.14 | Apr 12 2017

TOP STORY

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency

Scientists showed that a chemical cocktail enabled the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem cells, which were capable of chimerizing both embryonic and extraembryonic tissues. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Induced Pluripotent Stem Cell Differentiation Enables Functional Validation of GWAS Variants in Metabolic Disease

The authors describe an approach to functionally validate identified variants through differentiation of induced pluripotent stem cells (iPSCs) to study cellular pathophysiology. They differentiated 68 iPSC lines into hepatocytes and adipocytes to investigate the effect of the 1p13 rs12740374 variant on cardiometabolic disease phenotypes via transcriptomics and metabolomic signatures. [Cell Stem Cell] Abstract | Graphical Abstract

Aberrant DNA Methylation in Human iPSCs Associates with MYC-Binding Motifs in a Clone-Specific Manner Independent of Genetics

To examine whether aberrant methylation results from genetic variation or non-genetic mechanisms, scientists generated human induced pluripotent stem cells (iPSCs) from monozygotic twins to investigate how genetic background, clone, and passage number contribute. They found that aberrantly methylated CpGs are enriched in regulatory regions associated with MYC protein motifs and affect gene expression. [Cell Stem Cell] Abstract | Graphical Abstract

Delayed Accumulation of H3K27me3 on Nascent DNA Is Essential for Recruitment of Transcription Factors at Early Stages of Stem Cell Differentiation

Investigators performed single-cell and gene-specific analyses and revealed that during the first hours of induction of differentiation of mammalian embryonic stem cells, accumulation of the repressive histone mark H3K27me3 is delayed after DNA replication, indicative of a decondensed chromatin structure in all regions of the replicating genome. This delay provides a critical “window of opportunity” for recruitment of lineage-specific transcription factors to DNA. [Mol Cell] Abstract | Graphical Abstract

Modeling Developmental and Tumorigenic Aspects of Trilateral Retinoblastoma via Human Embryonic Stem Cells

Researchers developed a model to study the role of retinoblastoma-1 (RB1) in early development and tumor formation by generating RB1-null human embryonic stem cells (hESCs) using CRISPR/Cas9. RB1^−/− hESCs initiated extremely large teratomas, with neural expansions similar to those of trilateral retinoblastoma tumors, in which retinoblastoma is accompanied by intracranial neural tumors. [Stem Cell Reports] Full Article | Graphical Abstract

Promyelocytic Leukemia Protein Is an Essential Regulator of Stem Cell Pluripotency and Somatic Cell Reprogramming

The authors report that promyelocytic leukemia protein (PML) contributes to embryonic stem cells (ESC) self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibited morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state. [Stem Cell Reports] Full Article | Graphical Abstract

Loss of Polycomb Group Protein Pcgf1 Severely Compromises Proper Differentiation of Embryonic Stem Cells

Investigators disrupted the Pcgf1, also known as Nspc1 and one of six Pcgf paralogs, in mouse embryonic stem cells by using CRISPR/Cas9 technology. They showed that although these mutant cells were viable and retained normal self-renewal, they displayed severe defects in differentiation in vitro. [Sci Rep] Full Article

EpCAM Intracellular Domain Promotes Porcine Cell Reprogramming by Upregulation of Pluripotent Gene Expression via Beta-Catenin Signaling

Scientists found that epithelial cell adhesion molecule (EpCAM) was undetectable in fibroblasts, but highly expressed in porcine induced pluripotent stem cells. They noticed that increasing EpCAM’s intercellular domain (EpICD) only was unable to improve activity of EpCAM targeted genes, but by blocking GSK-3 signaling and stabilizing beta-catenin signaling, EpICD could then significantly stimulate the promoter activity. [Sci Rep] Full Article

Scalable Stirred Suspension Culture for the Generation of Billions of Human Induced Pluripotent Stem Cells Using Single-Use Bioreactors

The authors investigated stirred suspension culture vessels for their suitability in the expansion of two human induced pluripotent stem cell (hiPSC) lines inoculated as a single cell suspension, with free scalability. In both spinner flasks and bioreactors, they expanded 16 × 10⁶ hiPSCs into 2 × 10⁹ hiPSCs in 14 days. [J Tissue Eng Regen Med] Abstract

Chick Derived Induced Pluripotent Stem Cells by the Poly-Cistronic Transposon with Enhanced Transcriptional Activity

To establish chick induced pluripotent stem (iPS) cells, researchers used six factors within the poly-cistronic reprogramming vector (PB-R6F), containing M3O, Sox2, Klf4, c-Myc, Lin28, and Nanog. The PB-R6F derived iPS cells were alkaline-phosphatase and SSEA-1 positive, which are markers of pluripotency. Histological analysis of teratoma revealed that the established chick iPS cells had the ability to differentiate into three-germ-layer derived tissues. [J Cell Physiol] Abstract

Human Stem Cell Modeling in Neurofibromatosis Type 1 (NF1)

The authors discuss the generation and potential applications of induced pluripotent stem cell technology to the study of NF1. [Exp Neurol] Abstract

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

Mission Therapeutics and University of Oxford Awarded Research Grant from the Michael J. Fox Foundation

Mission Therapeutics announced that it has been awarded a grant from the Michael J. Fox Foundation for Parkinson’s Research. This research grant will support the testing of Mission Therapeutics’ potent and selective USP30-targeted inhibitors in translationally relevant stem cell-derived Parkinson’s disease models. [Mission Therapeutics] Press Release

BioTime Forms New Subsidiary AgeX Therapeutics, Inc. to Develop Its Programs Focused on Human Aging

BioTime, Inc. announced the formation of AgeX Therapeutics, Inc., which will consolidate certain BioTime subsidiaries and programs in the field of interventional gerontology. The formation of AgeX will focus resources on the continued clinical development of its two lead programs; Renevia^® and OpRegen^®. [BioTime, Inc.] Press Release

U.S. Report Calls for Research Integrity Board

The U.S. research community needs to do a better job of both investigating misconduct allegations and promoting ethical conduct—or the government might act unilaterally in ways that scientists won’t like. That’s the implicit message sent by a new report out from the National Academies of Science, Engineering, and Medicine entitled Fostering Integrity in Research. [ScienceInsider] Editorial

Review of Canadian Science Calls for Better Oversight, Coordination — and More Money

To reinvigorate its science base, Canada needs to “reinvest” almost CAD $500 million in basic, investigator-led research over the next four years, according to a long-awaited review of the country’s science and innovation landscape. [ScienceInsider] Editorial

NEW Quantitative Principles in Biology
November 2-4, 2017
Heidelberg, Germany

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

NEW Postdoctoral Position – Epigenetics of Pluripotent Stem Cells (Albert Einstein College of Medicine)

NEW Research Scientist – Stem Cell Biology (ArunA Biomedical, Inc.)

Research Associate – Research and Development (STEMCELL Technologies, Inc.)

Postdoctoral Fellow – Epigenetic Mechanisms (European Molecular Biology Laboratory)

Postdoctoral Fellow – Stem Cells and Epigenetics (University of Michigan)

Postdoctoral Fellow – Transcriptional Networks (Radboud University)

Postdoctoral Fellow – Somatic Variation (Wellcome Trust Sanger Institute)

Independent Group Leaders – Regenerative Medicine (Center for Regenerative Medicine)

Group Leader – Induced Pluripotent Stem Cells and Brain Malignancies (German Cancer Research Center)

Postdoctoral Research Associate – Developmental Neuroscience (University of Nebraska Medical Center)

Postdoctoral Fellow – Bone Regeneration and Stem Cell Biology (New York University Medical Center)

Postdoctoral Fellow – Stem Cell Research (Ecole Polytechnique Fédérale de Lausanne)

Postdoctoral Fellow – Multiple Areas (University of Oklahoma)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Pluripotent Stem Cell Technology (University of California, Davis)

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