ESC & iPSC News Volume 14.16 | May 1 2019

TOP STORY

Cell Competition during Reprogramming Gives Rise to Dominant Clones

A cellular barcoding strategy, whereby heritable DNA tags were inserted into the genome of mouse embryonic fibroblasts, was used to track the relative contribution of clonal derivatives to the reprogramming population. Mathematical modeling was used to decouple the effect of stochastic reprogramming latencies on clonal dynamics, enabling the identification of non-neutral clonal dominance. [Science] Abstract

(Ranked by impact factor of the journal)

Direct Induction of the Three Pre-Implantation Blastocyst Cell Types from Fibroblasts

By utilizing a sophisticated fluorescent knockin reporter system, researchers identified a combination of five transcription factors, Gata3, Eomes, Tfap2c, Myc, and Esrrb, that could reprogram fibroblasts into iPSCs, induced trophoblast stem cells, and induced extraembryonic endoderm stem cells, concomitantly. In-depth transcriptomic, chromatin, and epigenetic analyses provided insights into the molecular mechanisms that underlie the reprogramming process toward the three cell types. [Cell Stem Cell] Full Article | Graphical Abstract

Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency

Investigators delineated additional contributions of the ETS-family transcription factor ETV5 and the repressor RBPJ. In response to ERK signaling, ETV5 switched activity from supporting self-renewal and underwent genome relocation linked to commissioning of enhancers activated in formative epiblast. Independent upregulation of RBPJ prevented re-expression of potent naive factors, TBX3 and NANOG, to secure exit from the naive state. [Cell Stem Cell] Full Article | Graphical Abstract

Epigenetic Modulation of a Hardwired 3D Chromatin Landscape in Two Naive States of Pluripotency

Using integrative and time-resolved analyses the authors showed that the extensive transcriptome and epigenome resetting during the conversion between ‘serum’ and ‘2i’ states of mouse ESCs took place with minimal enhancer-promoter rewiring that became more evident in primed-state pluripotency. Instead, differential gene expression was strongly linked to enhancer activation via H3K27ac. [Nat Cell Biol] Abstract

Functional Landscape of PCGF Proteins Reveals Both RING1A/B-Dependent- and RING1A/B-Independent-Specific Activities

Scientists showed that PCGF1 and PCGF2 largely compensated for each other, while other PCGF proteins had high levels of specificity for distinct target genes. PCGF2 associated with transcription repression, whereas PCGF3 and PCGF6 associated with actively transcribed genes. Notably, PCGF3 and PCGF6 complexes could assemble and be recruited to several active sites independently of RING1A/B activity. [Mol Cell] Full Article | Graphical Abstract

Synergy between Variant PRC1 Complexes Defines Polycomb-Mediated Gene Repression

Researchers used combinatorial genetic perturbation coupled with quantitative genomics to discover the central determinants of Polycomb-mediated gene repression in mouse embryonic stem cells. They demonstrated that canonical Polycomb repressive complex 1 (PRC1), which mediated higher-order chromatin structures, contributed little to gene repression. Instead, they uncovered an unexpectedly high degree of synergy between variant PRC1 complexes, which was fundamental to gene repression. [Mol Cell] Full Article | Graphical Abstract

Asymmetric Division Events Promote Variability in Cell Cycle Duration in Animal Cells and Escherichia coli

Investigators identified among sibling cells an outlier using hierarchical clustering on cell cycle durations of granddaughter cells obtained by lineage tracking of single histone2B-labelled MDCKs. Remarkably, divisions involving outlier cells were not uniformly distributed in lineages, as shown by permutation tests, but appeared to emerge from asymmetric divisions taking place at non-stochastic levels. [Nat Commun] Full Article

Human Pre-Valvular Endocardial Cells Derived from Pluripotent Stem Cells Recapitulate Cardiac Pathophysiological Valvulogenesis

The authors report that, by combining single cell sequencing and in vivo approaches, a population of human pre-valvular endocardial cells (HPVCs) could be derived from pluripotent stem cells. HPVCs expressed gene patterns conforming to the E9.0 mouse atrio-ventricular canal endocardium signature. [Nat Commun] Full Article

The Cell-Surface Marker Sushi Containing Domain 2 Facilitates Establishment of Human Naive Pluripotent Stem Cells

Scientists report that Sushi Containing Domain 2 (SUSD2) was a robust cell-surface marker of naive human PSCs (hPSCs) in the embryo and in vitro. SUSD2 transcripts were enriched in the pre-implantation epiblast of human blastocysts and immunostaining showed localization of SUSD2 to KLF17-positive epiblast cells. SUSD2 mRNA was strongly expressed in naive hPSCs but was negligible in other hPSCs. [Stem Cell Reports] Full Article

Discovery and Characterization of Variance QTLs in Human Induced Pluripotent Stem Cells

Investigators took a genome-wide approach to identify expression variance quantitative trait loci (QTL). To this end, they generated single cell RNA-seq (scRNA-seq) data from iPSCs derived from 53 Yoruba individuals. They collected data for a median of 95 cells per individual and a total of 5,447 single cells, and identified 235 mean expression QTLs at 10% FDR, of which 79% replicate in bulk RNA-seq data from the same individuals. [PLoS Genet] Full Article

OCT4 and PAX6 Determine the Dual Function of SOX2 in Human ESCs as a Key Pluripotent or Neural Factor

The authors studied the role of SOX2 in human ESCs (hESCs) by gain- and loss-of-function approaches and explored the possible underlying mechanisms. They demonstrated that knockdown of SOX2 induced hESC differentiation to endoderm-like cells, whereas overexpression of SOX2 in hESCs enhanced their pluripotency under self-renewing culture conditions but promoted their neural differentiation upon replacing the culture to non-self-renewal conditions. [Stem Cell Res Ther] Full Article

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Astrocyte Alterations in Neurodegenerative Pathologies and Their Modeling in Human Induced Pluripotent Stem Cell Platforms

Scientists focus on the role of astrocytes in human neurodegenerative disease and the potential of the novel stem cell-based platforms in modeling astrocytic functions in health and in disease. [Cell Mol Life Sci] Full Article

Concise Review: Genetic and Epigenetic Regulation of Cardiac Differentiation from Human Pluripotent Stem Cells

The authors review cardiac differentiation protocols and their molecular machinery, closing with a discussion of the future challenges for producing human pluripotent stem cell-derived cardiomyocytes. [Stem Cells] Abstract | Full Article

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

StemoniX^® Announces Collaborative Research Agreement with the NIH’s National Center for Advancing Translational Sciences (NCATS)

StemoniX^® Inc. announced that it entered into a research collaboration agreement with NCATS to screen a library of neuronal signaling and opioid compounds using microBrain 3D as part of the NIH Helping to End Addiction Long-term^SM Initiative, a trans-NIH effort to advance national priorities in addressing the opioid crisis through science. [StemoniX] Press Release

Cell Microsystems Receives New NIH Grants for Automating CRISPR Workflows

Cell Microsystems announced it has received two NIH Small Business Innovation and Research awards totaling $1.9 million to automate CRISPR workflows using its proprietary CellRaft Technology. [Cell Microsystems (Business Wire, Inc.)] Press Release

In Lopsided Vote, US Science Academy Backs Move to Eject Sexual Harassers

Breaking with their 156-year history, members of the US National Academy of Sciences (NAS) voted overwhelmingly in favor of amending the elite organization’s bylaws to allow ejection of members who breach the group’s new Code of Conduct, which outlines offenses including sexual harassment. Historically, membership in NAS has been an honor conferred for life. [ScienceInsider] Editorial

Thousands of Scientists in Argentina Strike to Protest Budget Cuts

Scientists from labs across Argentina stayed home, joining a nationwide strike against the government’s latest round of austerity measures. One of their key rallying points: a call to restore lost opportunities for young researchers who began their education during a time of high investment in science but now have little hope of continuing their careers in Argentina. [ScienceInsider] Editorial

House Democrats Move to Resurrect Congress’s Science Advisory Office

Democrats in the US House of Representatives want to bring back Congress’s long-dead science advice office. A draft funding bill released today calls for providing $6 million to re-establish the Office of Technology Assessment, which Republican lawmakers killed in 1995. [ScienceInsider] Editorial

NEW Understanding the Molecular Mechanisms that Underpin Wound Repair and Regeneration
June 9-14, 2019
New London, New Hampshire, United States

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NEW Postdoctoral Associate – Stem Cell Differentiation in Immunology (University of Massachusetts Medical School)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

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

Research Assistant – Stem Cells & Regenerative Medicine (Boston Children’s Hospital)

Postdoctoral Fellow – Pluripotent Stem Cells & Joint Tissue Development (Boston Children’s Hospital)

Postdoctoral Lecturer – Stem Cell Biology & Regenerative Medicine (The University of Manchester)

Postdoctoral Fellowship – iPSCs and Differentiated Neurons (Howard Hughes Medical Institute)

Postdoctoral Fellowship – Cell Fate and Cancer Initiation (University of Miami Miller School of Medicine)

Associate Staff Scientist, Automation Systems (New York Stem Cell Foundation)

Postdoctoral Position – Human Pluripotent Stem Cell Biology (Washington University School of Medicine)

Postdoctoral Positions – Epigenetics of Stem Cells, Development and Cancer (Albert Einstein College of Medicine)

Staff Scientist – Transcriptional Control in Development and Disease (Fred Hutchinson Cancer Research Center)

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

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

Postdoctoral Fellowship – Human iPSC Research (Emory University)

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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