ESC & iPSC News Volume 12.24 | Jun 21 2017

TOP STORY

Researchers Develop First-Ever Human Tissue Platform to Test Drugs for Colon Cancer

The first-ever “disease in a Petri dish” platform that models human colon cancer derived from stem cells has been developed by investigators, allowing them to identify a targeted drug treatment for a common, inherited form of the disease. The discovery also overcomes a longstanding challenge of using mice to research this form of cancer, as they do not typically develop the disease. [Press release from Weill Cornell Medicine discussing online prepublication in Nature Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Single-Cell Multi-Omics Sequencing of Mouse Early Embryos and Embryonic Stem Cells

Researchers developed a single-cell multi-omics sequencing technology that can analyze the chromatin state/nucleosome positioning, DNA methylation, copy number variation and ploidy simultaneously from the same individual mammalian cell. They used this method to analyze the reprogramming of the chromatin state and DNA methylation in mouse preimplantation embryos. [Cell Res] Full Article

p53 Is Essential for DNA Methylation Homeostasis in Naïve Embryonic Stem Cells, and Its Loss Promotes Clonal Heterogeneity

The authors report that, in naïve mouse embryonic stem cells (mESCs), p53 restricted the expression of the de novo DNA methyltransferases Dnmt3a and Dnmt3b while up-regulating Tet1 and Tet2, which promote DNA demethylation. The DNA methylation imbalance in p53-deficient mESCs was the result of augmented overall DNA methylation as well as increased methylation landscape heterogeneity. [Genes Dev] Abstract

High Autophagic Flux Guards ESC Identity through Coordinating Autophagy Machinery Gene Program by FOXO1

Scientists identified high autophagic flux as an essential mechanism to maintain ESC identity. They showed that mouse ESCs exhibit a high autophagic flux that is maintained by coordinating expression of autophagy core molecular machinery genes through FOXO1, a forkhead family transcription factor. [Cell Death Differ] Abstract

A Strong Contractile Actin Fence and Large Adhesions Direct Human Pluripotent Colony Morphology and Adhesion

Researchers imaged human PSCs at the cell-extracellular matrix interface with total internal reflection fluorescence microscopy and discovered that adhesions at the colony edge were exceptionally large and connected by thick ventral stress fibers. The actin fence encircling the colony was found to exert extensive Rho-ROCK-myosin-dependent mechanical stress to enforce colony morphology, compaction, and pluripotency and to define mitotic spindle orientation. [Stem Cell Reports] Full Article | Graphical Abstract

TEC Controls Pluripotency and Early Cell Fate Decisions of Human Pluripotent Stem Cells via Regulation of FGF2 Secretion

Human pluripotent stem cells (hPSCs) require signaling provided by fibroblast growth factor (FGF) receptors. This can be initiated by the recombinant FGF2 ligand supplied exogenously, but hPSCs further support their niche by secretion of endogenous FGF2. The authors describe a role of tyrosine kinase expressed in hepatocellular carcinoma (TEC) kinase in this process. [Stem Cells] Abstract

Disrupting Interactions between β-Catenin and Activating TCFs Reconstitutes Ground State Pluripotency in Mouse Embryonic Stem Cells

Researchers investigated whether replacing CHIR with iCRT3, a small molecule that abrogates β-catenin–TCF interaction, can still retain ground state pluripotency in mouse ESCs. Their data suggests that iCRT3 + PD mediated coinhibition of MEK and β-catenin/TCF-dependent transcriptional activity over multiple passages significantly reduces expression of differentiation markers, as compared to 2i. [Stem Cells] Abstract

Sensitivity of Human Pluripotent Stem Cells to Insulin Precipitation Induced by Peristaltic Pump-Based Medium Circulation: Considerations on Process Development

Controlled large-scale production of human pluripotent stem cells (hPSCs) is indispensable for their envisioned clinical translation. Aiming at advanced process development in suspension culture, the sensitivity of hPSC media to continuous peristaltic pump-based circulation, a well-established technology extensively used in hydraulically-driven bioreactors, was investigated. [Sci Rep] Full Article

Generation of Tooth–Periodontium Complex Structures Using High-Odontogenic Potential Dental Epithelium Derived from Mouse Embryonic Stem Cells

The authors established an optimized approach to induce high-odontogenic potential dental epithelium derived from mouse embryonic stem cells by temporally controlling bone morphogenic protein 4 function and regenerated tooth–periodontium complex structures in vivo. [Stem Cell Res Ther] Full Article

Exposure of Induced Pluripotent Stem Cell-Derived Vascular Endothelial and Smooth Muscle Cells in Coculture to Hemodynamics Induces Primary Vascular Cell-Like Phenotypes

Human iPSCs can be differentiated into vascular endothelial (iEC) and smooth muscle (iSMC) cells. Scientists tested the hypothesis that hemodynamic exposure of iECs in coculture with iSMCs induces an in vivo-like phenotype. Hemodynamic flow-induced gene expression positively correlated between primary endothelial cells and iECs, as well as primary smooth muscles cells and iSMCs. [Stem Cells Transl Med] Full Article

Nanog Fluctuations in Embryonic Stem Cells Highlight the Problem of Measurement in Cell Biology

Using a combination of mathematical modeling and experiment, investigators showed that there are unforeseen ways in which widely used reporter strategies can systematically disturb the dynamics they are intended to monitor, sometimes giving profoundly misleading results. [Biophys J] Full Article

Stem Cell Models of Alzheimer’s Disease: Progress and Challenges

iPSC-neuron models have been widely employed to model Alzheimer’s disease (AD) and the authors discuss the progress that has been made to date using patient-derived neurons to recapitulate key aspects of AD pathology and how these models have contributed to a deeper understanding of AD molecular mechanisms, as well as addressing the key challenges posed by using this technology and what progress is being made to overcome these. [Alzheimers Res Ther] Full Article

iPSC Technology-Based Regenerative Therapy for Diabetes

The directed differentiation of human PSCs, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), into pancreatic endocrine lineages has been vigorously examined by reproducing the in vivo developmental processes of pancreas. Recent advances in this research field have enabled the generation from hESCs/iPSCs of functionally mature β-like cells in vitro that show glucose-responsive insulin secretion ability. [J Diabetes Investig] Abstract | Full Article

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BioTime’s Renevia^™ Achieves Primary Endpoint in European Pivotal Trial

BioTime, Inc. reported that, based on the analysis of top line data, the Renevia^™ pivotal trial in Europe has met its primary endpoint. The primary endpoint was the change in hemifacial volume at six months in the treated patients compared to patients in the delayed treatment arm as measured by 3D photographic volumetric assessment. [BioTime, Inc.] Press Release

MilliporeSigma Expands Distribution Agreement with Public Health England

MilliporeSigma announced an expansion of its distribution alliance with Public Health England to include the European Bank for iPSCs — a comprehensive iPSC bank of more than 300 quality-controlled, disease-relevant, patient-derived human iPSC lines. [EMD Millipore Corporation] Press Release

He Broke Ground in Stem-Cell Research. Now He’s Running for Congress.

Stem-cell researcher Hans Keirstead, 50, announced last week that he will try to unseat California’s Rep. Dana Rohrabacher. Keirstead, a Democrat with a PhD in neuroscience from the University of British Columbia, was a professor at the University of California at Irvine before launching and selling several biotech companies. [The Washington Post] Editorial

University of Tokyo Scientist Hit by Anonymous Allegations Fights Back

Last September, anonymous allegations of questionable data and images in 22 papers by six prominent groups at the prestigious University of Tokyo prompted the school to set up an investigating committee. Now, even before the panel completes its investigation, one of the accused researchers has mounted a staunch defense of his work, with a point-by-point rebuttal of the allegations and an apology for mistakes confirmed in several of the questioned papers. [ScienceInsider] Editorial

China Cracks Down on Fake Peer Reviews

The Chinese government is going on the offensive against scientists who dupe journals by creating fraudulent reviews of submitted papers. A coalition of agencies led by the science ministry announced that the government would suspend the grants of researchers involved in such fraud, which surfaced earlier this year when a cancer journal retracted 107 research papers from Chinese authors. [Nature News] Editorial

Strengthened US Sanctions on Cuba Disappoint Scientists

US President Donald Trump announced that he would strengthen travel and trade restrictions against Cuba, reversing his predecessor’s attempts to normalize relations with the country. The move is a blow to scientists who hoped that former president Barack Obama’s push to relax US restrictions on Cuba would make it easier for researchers there to travel and to collaborate with colleagues in the United States. [Nature News] Editorial

NEW Keystone Symposia: Lymphocytes and Their Roles in Cancer
February 11-15, 2018
Keystone, Colorado, United States

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NEW Laboratory Research Technician – Epigenetics of Stem Cells (Albert Einstein College of Medicine)

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

Scientific Sales Representative – Media (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Bioinformatics of Single Cell Genomics (Institute of Molecular Biology)

Postdoctoral Fellow – Bioinformatics (Stanford University)

Senior/Principle Research Associate – Cell and Molecular Biology (Editas Medicine)

Assistant Professor – Stem Cell and Regenerative Biology (Harvard University)

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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