ESC & iPSC News Volume 14.19 | May 22 2019

TOP STORY

Genome-Scale Screens Identify JNK-JUN Signaling as a Barrier for Pluripotency Exit and Endoderm Differentiation

The Jun N-terminal kinase (JNK)-JUN pathway did not act through directly inhibiting definitive endoderm (DE) enhancers. Instead, JUN co-occupied ESC enhancers with OCT4, NANOG, SMAD2 and SMAD3, and specifically inhibited the exit from the pluripotent state by impeding the decommissioning of ESC enhancers and inhibiting the reconfiguration of SMAD2 and SMAD3 chromatin binding from ESC to DE enhancers. [Nat Genet] Abstract

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Functional Cardiac Fibroblasts Derived from Human Pluripotent Stem Cells via Second Heart Field Progenitors

Scientists showed differentiation of human PSCs (hPSCs) using sequential modulation of Wnt and FGF signaling to generate second heart field progenitors that efficiently give rise to hPSC-cardio fibroblasts (CFs). The hPSC-CFs resembled native heart CFs in cell morphology, proliferation, gene expression, fibroblast marker expression, production of extracellular matrix and myofibroblast transformation induced by TGFβ1 and angiotensin II. [Nat Commun] Full Article

Wnt Signaling Separates the Progenitor and Endocrine Compartments during Pancreas Development

To uncover in vitro autonomous responses, scientists performed single-cell RNA sequencing on human ESCs as they differentiated in spherical clusters. They observed that endocrine cells and their progenitors existed beside one another in separate compartments that activated distinct genetic pathways. [Cell Rep] Full Article | Graphical Abstract

Universal Correction of Blood Coagulation Factor VIII in Patient-Derived Induced Pluripotent Stem Cells Using CRISPR/Cas9

Investigators report a universal approach to correct the various mutations in hemophilia A patient iPSCs by the targeted insertion of the blood coagulation factor VIII gene into the human H11 site via CRISPR/Cas9. They derived corrected clones from two types of patient iPSCs with frequencies of up to 64% and 66%, respectively, without detectable unwanted off-target mutations. [Stem Cell Reports] Full Article

A Human Pluripotent Stem Cell-Based Screen for Smooth Muscle Cell Differentiation and Maturation Identifies Inhibitors of Intimal Hyperplasia

To generate more contractile smooth muscle cells, the authors performed a high-throughput differentiation screen using a MYH11-NLuc-tdTomato human ESC reporter cell line. They identified RepSox as a factor that promoted differentiation of MYH11-positive cells by promoting NOTCH signaling. [Stem Cell Reports] Full Article | Press Release

Clonal Isolation of Human Pluripotent Stem Cells on Nanofibrous Substrates Reveals an Advanced Subclone for Cardiomyocyte Differentiation

A nanofibrous platform was developed for single human IPSC isolation and culture. One type of single cell-derived subclone was established and found to have a distinct morphology compared to other subclones. When used for differentiation toward cardiomyocytes, this type of subclone demonstrated higher differentiation efficiency, increased maturation, and stronger beating compared to those derived from the other subclones. [Adv Healthc Mater] Abstract

Quantified Forces between HepG2 Hepatocarcinoma and WA07 Pluripotent Stem Cells with Natural Biomaterials Correlate with In Vitro Cell Behavior

A colloidal probe microscopy technique was used to quantify the interactions of two cell lines with natural, xeno-free biomaterials of different chemistry, morphology, and origin. Key components of extracellular matrices, as well as wood-derived, cellulose nanofibrils were analyzed. [Sci Rep] Full Article

Highly Efficient Induction of Primate iPS Cells by Combining RNA Transfection and Chemical Compounds

The authors report that marmoset cells were efficiently reprogrammed into iPS cells by combining RNA transfection and chemical compounds. Using this novel combination, they generated transgene integration-free marmoset iPS cells from a variety of cells that were difficult to reprogram using conventional RNA transfection method. [Genes Cells] Abstract

A Critical E-Box in Barhl1 3′ Enhancer Is Essential for Auditory Hair Cell Differentiation

Through data mining and an in vitro report assay, researchers identified Barhl1 as a direct target gene of Atoh1 and one E-box (E3) in Barhl1 3’ enhancer was crucial for Atoh1-mediated Barhl1 activation. Then they generated a mouse ESC (mESC) line carrying disruptions on this E3 site E-box using CRISPR/Cas9 technology and this E3 mutated mESC line was further subjected to an efficient stepwise hair cell differentiation strategy in vitro. [Cells] Full Article

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Epigenetic Aberrations in Human Pluripotent Stem Cells

The authors highlight frequent epigenetic aberrations found in human (h) PSCs, including alterations in DNA methylation patterns, parental imprinting, and X chromosome inactivation. They discuss the potential origins of these abnormalities in human ESCs and iPSCs, survey the different methods for detecting them, and elaborate on their potential consequences for the different utilities of hPSCs. [EMBO J] Abstract

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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 ESC lines has been reached. [Novo Nordisk] Press Release

Pershing Square Sohn Prize Awards $4.2M to Seven “Next Generation” Innovators in Cancer Research

The Pershing Square Sohn Cancer Research Alliance announced the seven winners of the 2019 Pershing Square Sohn Prize for Young Investigators in Cancer Research, awarded annually to talented New York City-area cancer research scientists and physician-scientists. The prize, totaling $4.2 million in funding awarded, emboldens early-career investigators to pursue research projects at a stage when traditional funding is lacking. [The Pershing Square Foundation] Press Release

NSF, NASA, NIST Would Get Funding Boosts under House Spending Bill

The National Science Foundation (NSF) would get a 7% budget increase, and NASA a 3.8% bump, under a 2020 spending bill approved by an appropriations panel of the US House of Representatives. The bill rejects cuts to those and other federal research agencies proposed by President Donald Trump’s administration. [ScienceInsider] Editorial

China Set to Introduce Gene-Editing Regulation Following CRISPR-Baby Furore

China is poised to introduce a new regulation on gene editing in humans. A draft of the country’s new civil code lists human genes and embryos in a section on personality rights to be protected. Experiments on genes in adults or embryos that endanger human health or violate ethical norms can accordingly be seen as a violation of a person’s fundamental rights. [Nature News] Editorial

National Cancer Institute Will Stop Funding Nanotechnology Centers

The end to funding represents a “natural transition” from putting dedicated support into an emerging field to becoming a more mature research field that fits in with other cancer fields, says Piotr Grodzinski of the National Cancer Institute’s Nanodelivery Systems and Devices Branch, which oversees the Centers of Cancer Nanotechnology Excellence, to Science. [The Scientist] Editorial

NEW Stem Cells UK
October 1, 2019
London, United Kingdom

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NEW Cell Culture Technician – Pluripotent Stem Cell Biology (University of Southhampton)

NEW Postdoctoral Associate – RNA Genomics in IPSCs (The Jackson Laboratory)

NEW Postdoctoral Fellow – Stem Cells and Regenerative Medicine (German Research Center for Environmental Health)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

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

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

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

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