ESC & iPSC News Volume 14.10 | Mar 20 2019

TOP STORY

A Human iPSC Double-Reporter System Enables Purification of Cardiac Lineage Subpopulations with Distinct Function and Drug Response Profiles

The authors report the generation of a human iPSC TBX5 ^Clover2 and NKX2-5 ^TagRFP double reporter to delineate cardiac lineages and isolate lineage-specific subpopulations. Molecular analyses revealed that four different subpopulations could be isolated based on the differential expression of TBX5 and NKX2-5, mimicking the first heart field, epicardial, second heart field, and endothelial lineages. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Human Induced Pluripotent Stem Cell Model of Trastuzumab-Induced Cardiac Dysfunction in Breast Cancer Patients

Investigators employed a human iPSC-derived cardiomyocyte (iPSC-CM) platform to determine the underlying cellular mechanisms in trastuzumab-induced cardiac dysfunction. They assessed the effects of trastuzumab on structural and functional properties in iPSC-CMs from healthy individuals and performed RNA-sequencing to further examine the effect of trastuzumab on iPSC-CMs. [Circulation] Abstract

Glycolysis Regulates Human Embryonic Stem Cell Self-Renewal under Hypoxia through HIF-2α and the Glycolytic Sensors CTBPs

Researchers demonstrated a direct interaction between hypoxia-inducible factor 2α (HIF-2α) and the C-terminal binding protein proximal promoters in human ESCs (hESCs) cultured only under hypoxia. Decreasing the rate of flux through glycolysis in hESCs maintained under hypoxia resulted in a reduction of C-terminal binding proteins (CTBPs), OCT4, SOX2, and NANOG, but also in the expression of HIF-2α. [Stem Cell Reports] Full Article

WDR5, BRCA1, and BARD1 Co-Regulate the DNA Damage Response and Modulate the Mesenchymal-to-Epithelial Transition during Early Reprogramming

Scientists revealed five morphological phenotypes in early reprogramming, including one displaying large round colonies exhibiting an early block of reprogramming. Using RNA sequencing, they identified transcriptional changes associated with these phenotypes. [Stem Cell Reports] Full Article | Graphical Abstract

Absence of Cyclin-Dependent Kinase Inhibitor p27 or p18 Increases Efficiency of iPSC Generation without Induction of iPSC Genomic Instability

The authors report the effects of absence of mouse p27 or p18 on iPSC generation efficiency and genomic stability. Expression levels of cyclin-dependent kinases inhibitors p21, p27, and p18 decreased during iPSC reprogramming. [Cell Death Dis] Full Article

Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy

An extragenic genomic safe harbor locus on chromosome 1 permitted robust transgene expression, but a 2 Mb-distant gene within the same topologically associated domain showed aberrant expression. Although knockin iPSCs carrying a suicide gene were sufficiently sensitive to ganciclovir in vitro, the resulting teratomas showed varying degrees of resistance to the drug in vivo. [Stem Cells Transl Med] Full Article

CXCL4/PF4 Is a Predictive Biomarker of Cardiac Differentiation Potential of Human Induced Pluripotent Stem Cells

Researchers aimed to identify biomarkers for predicting cardiac differentiation potential of human iPSC (hiPSC) lines by comparing the gene expression profiles of six undifferentiated hiPSC lines with different cardiac differentiation capabilities. Of the candidate genes, PF4 was validated as a biomarker expressed in undifferentiated hiPSCs with high potential for cardiac differentiation in 13 additional hiPSC lines. [Sci Rep] Full Article

Optimized Protocol for the Hepatic Differentiation of iPSCs in a Fluidic Microenvironment

The authors evaluated the performance of different protocols for the hepatic differentiation of human iPSCs in microfluidic biochips. Strategies for complete and partial on-chip differentiation were tested. Unlike full on-chip differentiation, the transfer of iPSCs from Petri dishes to biochips during the differentiation process produced a heterogeneous tissue with enhanced hepatic features compared to control cultures in Petri dishes. [Biotechnol Bioeng] Abstract

Media Composition Modulates Human Embryonic Stem Cell Morphology and May Influence Preferential Lineage Differentiation Potential

Human ESCs, maintained in diverse medias, demonstrated alterations in morphological parameters and subsequent alterations in underlying transcript expression and lineage differentiation. Analysis of morphological parameters showed distinct and significant differences between the undefined, less defined and Xeno-free medias while still maintaining pluripotency markers. [PLoS One] Full Article

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Studying Human Neurological Disorders Using Induced Pluripotent Stem Cells: From 2D Monolayer to 3D Organoid and Blood Brain Barrier Models

Investigators review and summarize the recent advances in modeling Alzheimer’s disease pathology and progression based on human PSC-derived neural cells, tissues, and brain organoids. They also cover the current status of applications of 2D, 3D, and blood-brain barrier models in drug screening, precision medicine, and modeling a wide range of neurological diseases. [Compr Physiol] Abstract

The Use of Pluripotent Stem Cell-Derived Organoids to Study Extracellular Matrix Development during Neural Degeneration

The authors review and summarize recent advances in modeling Alzheimer’s disease pathology and progression based on human PSC (hPSC)-derived neural cells, tissues, and brain organoids. In addition, they discuss the roles of extracellular matrices in neural differentiation of hPSCs and the influences of heparan sulfate proteoglycans, chondroitin sulfate proteoglycans, and hyaluronic acid on the progression of neurodegeneration. [Cells] Full Article

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

Canada’s Stem Cell Network Welcomes Renewed Federal Commitment for Stem Cell & Regenerative Medicine Research

Through Budget 2019, the Government of Canada has signaled its continued confidence in Canadian stem cell and regenerative medicine research with a multi-year investment of $18 million through the Stem Cell Network. [Stem Cell Network] Press Release

Stem Cell Model of Motor Neuron Disease Wins International 3Rs Prize 2018

A paper describing the use of patient-derived stem cells to study motor neuron disease has been recognised with the annual £30k prize awarded by the National Centre for the Replacement Refinement & Reduction of Animals in Research (NC3Rs) and sponsored by GSK. [National Centre for the Replacement Refinement & Reduction of Animals in Research] Press Release

Japan Poised to Allow ‘Reprogrammed’ Stem-Cell Therapy for Damaged Corneas

A Japanese committee has provisionally approved the use of reprogrammed stem cells to treat diseased or damaged corneas. Researchers are now waiting for final approval from the health ministry to test the treatment in people with corneal blindness, which affects millions of people around the world. [Nature News] Editorial

EU’s Biggest Research Program Yet Takes Shape

The European Union (EU)’s three governing institutions — the Parliament, Council and Commission — reached agreement in the small hours of 20 March on the outline of the EU’s next seven-year research-funding program. [Nature News] Editorial

Canada Budget Overlooks Basic Research

Canada’s 2019 budget, released on March 19^th, includes modest increases for Prime Minister Justin Trudeau’s government priorities, including neuroscience and genomics research ― nothing like the historic five-year, Can$4-billion boost for basic science and research unveiled in 2018. [Nature News] Editorial

US Researchers Hope Congress Will Dig NSF Out of a $1 Billion Budget Hole

For the second time in three years, President Donald Trump has recommended deep cuts to the National Science Foundation (NSF) in Alexandria, Virginia. And scientists are hoping Congress will again come to the agency’s rescue. [ScienceInsider] Editorial

NEW Cardiology World Conference: ‘Advances in Cardiology: Research and Innovations’
May 15-16, 2019
Tokyo, Japan

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

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

NEW Director of Operations – Biotech Production (Cincinnati Children’s Hospital Medical Center)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

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

Lecturer – iPSC Models of Neurological Disease (University College London)

Postdoctoral Fellowship – Patient-Derived iPSC Research (Oklahoma Medical Research Foundation)

Postdoctoral Fellowship – Human iPSC Research (Emory University)

Research Associate – iPSC & Neurodegenerative Disease (TU Dresden)

Postdoctoral Fellowship – Stem Cells & Drug Screening (Murdoch Children’s Research Institute)

Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

Postdoctoral Research Fellow – Discovery Oncology (Merck)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

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

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

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

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