ESC & iPSC News Volume 12.06 | Feb 15 2017

TOP STORY

Genome Editing in hPSCs Reveals GATA6 Haploinsufficiency and a Genetic Interaction with GATA4 in Human Pancreatic Development

The authors investigated the association between human GATA6 haploinsufficiency and a wide range of clinical phenotypes that include neonatal and adult-onset diabetes using CRISPR/Cas9-mediated genome editing coupled with human pluripotent stem cell (hPSC) directed differentiation. They found that loss of one GATA6 allele specifically affects the differentiation of human pancreatic progenitors from the early PDX1+ stage to the more mature PDX1+NKX6.1+ stage, leading to impaired formation of glucose-responsive β-like cells. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

G1 Cyclins Link Proliferation, Pluripotency and Differentiation of Embryonic Stem Cells

Progression of mammalian cells through the G1 and S phases of the cell cycle is driven by the D-type and E-type cyclins. According to the current models, at least one of these cyclin families must be present to allow cell proliferation. Scientists showed that several cell types can proliferate in the absence of all G1 cyclins. However, following ablation of G1 cyclins, embryonic stem cells attenuated their pluripotent characteristics, with the majority of cells acquiring the trophectodermal cell fate. [Nat Cell Biol] Abstract

Drug Discovery for Diamond-Blackfan Anemia Using Reprogrammed Hematopoietic Progenitors

The authors adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells from Diamond-Blackfan anemia (DBA) patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. [Sci Transl Med] Abstract | Press Release

High-Throughput Screening of Tyrosine Kinase Inhibitor Cardiotoxicity with Human Induced Pluripotent Stem Cells

Researchers used human induced pluripotent stem cell–derived cardiomyocytes, generated from 11 healthy individuals and two patients receiving cancer treatment, to screen U.S. Food and Drug Administration–approved tyrosine kinase inhibitors (TKIs) for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. Using this data, they generated a “cardiac safety index” to reflect the cardiotoxicities of existing TKIs. [Sci Transl Med] Abstract | Press Release

Stepwise Reprogramming of Liver Cells to a Pancreas Progenitor State by the Transcriptional Regulator Tgif2

Investigators report that the TALE homeoprotein TGIF2 acts as a developmental regulator of the pancreas versus liver fate decision and is sufficient to elicit liver-to-pancreas fate conversion both ex vivo and in vivo. [Nat Commun] Full Article | Press Release

Foxa2 Identifies a Cardiac Progenitor Population with Ventricular Differentiation Potential

Scientists report the identification of a progenitor population that gives rise primarily to cardiovascular cells of the ventricles and only to few atrial cells of the differentiated heart. These progenitors are specified during gastrulation, when they transiently express Foxa2, a gene not previously implicated in cardiac development. [Nat Commun] Full Article | Press Release

Speed and Segmentation Control Mechanisms Characterized in Rhythmically-Active Circuits Created from Spinal Neurons Produced from Genetically-Tagged Embryonic Stem Cells

Researchers constructed synthetic microphysical neural networks, called circuitoids, using precise combinations of spinal neuron subtypes derived from mouse stem cells. Circuitoids of purified excitatory interneurons were sufficient to generate oscillatory bursts with properties similar to in vivo central pattern generators. [Elife] Full Article | Press Release | Video

The SIN3A/HDAC Corepressor Complex Functionally Cooperates with NANOG to Promote Pluripotency

Investigators found that the SIN3A/HDAC corepressor complex maintains embryonic stem cell (ESC) pluripotency and promotes the generation of induced pluripotent stem cells (iPSCs). NANOG and SIN3A co-occupy transcriptionally active pluripotency genes in ESCs and also co-localize extensively at their genome-wide targets in pre-iPSCs. [Cell Rep] Full Article | Graphical Abstract

Rapid Differentiation of Human Pluripotent Stem Cells into Functional Neurons by mRNAs Encoding Transcription Factors

Efficient differentiation of human pluripotent stem cells (hPSCs) into neurons is paramount for disease modeling, drug screening, and cell transplantation therapy in regenerative medicine. Scientists report the capability of five transcription factors (TFs) toward this aim: NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. In contrast to previous methods that have shortcomings in their speed and efficiency, a cocktail of these TFs as synthetic mRNAs can differentiate hPSCs into neurons in seven days, judged by calcium imaging and electrophysiology. [Sci Rep] Full Article

Connexin30.3 Is Expressed in Mouse Embryonic Stem Cells and Is Responsive to Leukemia Inhibitory Factor

The authors observed the expression of 19 connexin (Cx) isoforms in the mouse embryonic stem cell line, EB3. Their expression patterns could be classified into either pluripotent state-specific, differentiating stage-specific, or non-specific Cxs. [Sci Rep] Full Article

Differentiation of Oligodendrocyte Progenitor Cells from Dissociated Monolayer and Feeder-Free Cultured Pluripotent Stem Cells

Scientists generated oligodendrocyte progenitor cells and mature oligodendrocytes within three months from monkey embryonic stem cells. The embryonic stem cell-derived oligodendrocytes exhibited in vitro myelinogenic potency with rat dorsal root ganglion neurons. [PLoS One] Full Article

Modeling Neurodevelopmental and Psychiatric Diseases with Human iPSCs

The author reviews the recent progress in the use of human induced pluripotent stem cells (iPSCs) for modeling neurodevelopmental and psychiatric disorders and developing novel therapeutic strategies, and discuss challenges in this rapidly moving field. [J Neurosci Res] Abstract

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

Merryman Wins $6M to Address Heart Disease with Arthritis Drug, Fund Other Research

A Vanderbilt biomedical engineering professor has garnered $6 million total in grants to determine how to treat heart valve disease, pulmonary hypertension and heart failure using drugs originally developed for rheumatoid arthritis and applying the lessons learned from failed weight loss drugs. [Vanderbilt University School of Engineering] Press Release

Cancer Research UK Announces Inaugural Grand Challenge Teams to Answer the Biggest Questions in Cancer

Cancer Research UK announces that four international teams are the first recipients of its global £100 million Grand Challenge competition, which aims to overcome the biggest challenges facing cancer researchers in a global effort to beat cancer sooner. [Cancer Research UK] Press Release | Video

Henrietta Lacks’s Family Wants Compensation for Her Cells

The eldest son of Henrietta Lacks wants compensation from Johns Hopkins University and possibly others for the unauthorized use of her cells in research that led to decades of medical advances. The cells taken from the 31-year-old after she died of an aggressive form of cervical cancer in 1951 were the first to live outside the body in a glass tube. They were dubbed the HeLa cells and have become the most widely used human cells that exist in scientific research. [The Washington Post] Editorial

US Science Advisers Outline Path to Genetically Modified Babies

Modified human embryos should be allowed if researchers meet strict criteria, says long-awaited National Academies report. [Nature News] Editorial

Debate Erupts over Plan to Create Another Online Destination for Biology Preprints

A plan to create a new repository for biomedical and biology preprints has earned the endorsement of nearly a dozen major science funders, including government agencies, major foundations, and research charities. But it also has sparked a debate about whether an existing preprint repository, bioRxiv.org, should be the natural home for such material. [ScienceInsider] Editorial

NEW Reversion of Primed hPSCs to Naïve-Like State Training Course
April 25-26, 2017
Vancouver, Canada

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

NEW Postdoctoral Fellow – Human Genome Editing (Johns Hopkins University School of Medicine)

NEW Research Associate – Bioengineering (STEMCELL Technologies, Inc.)

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

Postdoctoral Fellow – Computational Single Cell Genomics (University Medical Center Groningen)

Postdoctoral Position – Cellular Genetics (Wellcome Trust Sanger Institute)

Postdoctoral Associate – Epigenetic Drivers of Human Stem Cell Pluripotency and Differentiation (University of Miami)

Head Scientist – iPSC Research (Victor Chang Cardiac Research Institute)

Postdoctoral Fellows – Pluripotent Embryonic Stem Cells and Embryo Development (Oslo University Hospital)

Postdoctoral Fellow – Multiple Areas (University of Oklahoma)

Regulatory Support Scientist – Biological Product Development (Cook MyoSite, Inc.)

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

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

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

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in ESC & iPSC News? Click here to submit!

Comments or suggestions? Submit your feedback here.