ESC & iPSC News Volume 14.44 | Nov 13 2019

TOP STORY

Quality of Induced Pluripotent Stem Cells Is Dramatically Enhanced by Omitting What Was Thought to Be the Most Crucial Reprogramming Factor

Scientists showed that Oct4, a factor most commonly used for reprogramming, is detrimental for the quality of iPSCs. Omitting Oct4 from the reprogramming cocktail allowed for the generation of mouse iPSCs with the highest developmental potential reported to date. [Press release from the Max Planck Institute for Molecular Biomedicine in Münster discussing online prepublication in Cell Stem Cell] Press Release | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4

Researchers found that polycistronic expression of Sox2 and Klf4 was sufficient to induce pluripotency in the absence of exogenous Oct4, and the stoichiometry of Sox2 and Klf4 was essential. [Cell Rep] Full Article | Graphical Abstract

DNA Methylation Directs Polycomb-Dependent 3D Genome Re-Organization in Naive Pluripotency

The authors demonstrated that 3D genome organization was altered in small molecule inhibitors (2i), with chromatin decompaction at polycomb target loci and a loss of long-range polycomb interactions. By preventing DNA hypomethylation during the transition to the ground state, they were able to restore to ESC in 2i the H3K27me3 distribution, as well as polycomb-mediated 3D genome organization that is characteristic of primed ESCs grown in serum. [Cell Rep] Full Article | Graphical Abstract

AAV-Mediated Gene Augmentation Therapy Restores Critical Functions in Mutant PRPF31^+/- iPSC-Derived RPE Cells

Investigators hypothesized that PRPF31-related retinitis pigmentosa would be amenable to treatment by adeno-associated virus (AAV)-mediated gene augmentation therapy. To test this hypothesis, they used iPSCs with mutations in PRPF31 and differentiated them into retinal pigment epithelium (RPE) cells. [Mol Ther Methods Clin Dev] Abstract | Graphical Abstract | Full Article

Wnt Inhibition Facilitates RNA-Mediated Reprogramming of Human Somatic Cells to Naive Pluripotency

Scientists investigated conditions for transgene-free reprogramming of human somatic cells to naive pluripotency. They found that Wnt inhibition promoted RNA-mediated induction of naive pluripotency. [Stem Cell Reports] Full Article

Effects of Spaceflight on Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Structure and Function

Investigators utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to study the effects of microgravity on cell-level cardiac function and gene expression. The hiPSC-CMs were cultured aboard the International Space Station for 5.5 weeks and their gene expression, structure, and functions were compared with ground control hiPSC-CMs. [Stem Cell Reports] Abstract | Graphical Abstract | Press Release

A Transcriptomic Study of Williams-Beuren Syndrome Associated Genes in Mouse Embryonic Stem Cells

The authors generated mouse embryonic stem cells clones expressing each of the four human Williams-Beuren syndrome (WBS) genes found in the specific delated region 7q11.23 causative of the WBS. They generated at least three stable clones for each gene with stable integration in the ROSA26 locus of a tetracycline-inducible upstream of the coding sequence of the genet tagged with a 3xFLAG epitope. [Sci Data] Full Article

Sex-Dependent VEGF Expression Underlies Variations in Human Pluripotent Stem Cell to Endothelial Progenitor Differentiation

Sex-based differences were identified in a GSK3 inhibitor based endothelial progenitor differentiation protocol. While male human PSCs (hPSCs) efficiently differentiated into CD34⁺ CD31⁺ endothelial progenitors upon GSK3 inhibition, female hPSCs showed limited differentiation capacity using this protocol. [Sci Rep] Full Article

FOXH1 Is Regulated by NANOG and LIN28 for Early-Stage Reprogramming

Scientists found FOXH1 expression plays a significant role to enhance epithelial marker and suppress mesenchymal gene expression in OSKM-mediated human cell reprogramming. [Sci Rep] Full Article

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Clinical Translation of Pluripotent Stem Cell Therapies: Challenges and Considerations

The authors describe completed or ongoing trials of PSCs, discuss their potential mechanisms of action, and consider how to address the challenges required for them to become a major therapy, using heart repair as a case study. [Cell Stem Cell] Abstract

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Editas Medicine and Celgene Corporation Amend Existing Collaboration to Develop and Commercialize Autologous and Allogeneic T Cell Medicines for the Treatment of Cancer and Autoimmune Diseases

Editas Medicine, Inc. announced an amended collaboration with Celgene Corporation under which the parties may research, develop, and commercialize autologous and allogeneic alpha-beta T cell medicines for the treatment of cancer and autoimmune diseases. [Editas Medicine, Inc.] Press Release

Qrons Extends Sponsored Research Agreement with Dartmouth College

Qrons Inc. announced that it has extended the term of its Sponsored Research Agreement with Dartmouth College for an additional year with funding through July 14, 2020. [Qrons Inc.] Press Release

Italy to Launch National Agency for Research

Just two months after Italy underwent a crisis of government and established an alliance between two leading political parties, the left-of-center Democratic Party and the anti-establishment Five Star Movement, the country has announced plans to start a National Agency for Research to help oversee the distribution of federal funds. [The Scientist] Editorial

The Mental Health of PhD Researchers Demands Urgent Attention

Two years ago, a student responding to Nature’s biennial PhD survey called on universities to provide a quiet room for “crying time” when the pressures caused by graduate study become overwhelming. At that time, 29% of 5,700 respondents listed their mental health as an area of concern – and just under half of those had sought help for anxiety or depression caused by their PhD study. Things seem to be getting worse. [Nature News] Editorial

Why NIH Is Beefing Up Its Data Sharing Rules after 16 Years

The US National Institutes of Health last week released a draft policy that will require all investigators with NIH funding to make their data sets available to colleagues. For the first time, grantees holding any NIH-funded grant—not just those above a $500,000 threshold in direct costs—will need to submit a detailed plan for sharing data, including steps to protect the privacy of research subjects. [ScienceInsider] Editorial

NEW Gene- and Cell-Based Therapies: CRISPR, Stem Cells, and 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 Postdoctoral Associate – Stem Cell Research (University of Minnesota Twin Cities)

Faculty Position – Stem Cell Research (Yale University School of Medicine)

Multiple Positions – Stem Cell Biology (NIH NCATS Stem Cell Translation Laboratory)

Research Assistant – Stem Cells and Engineering (New York Blood Center)

Postdoctoral Researcher – CRISPR/Cas9 in ESCs (Institute of Molecular Biology GmbH)

Postdoctoral Researcher – iPSC Models in Neurology (IRIBHM)

Postdoctoral Scientist – Regenerative Medicine (Cedars-Sinai Medical Center)

PhD Position – Human Inducible Stem Cells (University of Fribourg)

Research Associate – Computational Image Analysis and AI (University of Bristol)

Assistant Specialist – Division of Cardiovascular Medicine (University of California, Davis)

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

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