ESC & iPSC News Volume 14.25 | Jul 3 2019

TOP STORY

Dynamic Genetic Regulation of Gene Expression during Cellular Differentiation

Investigators generated time-series RNA sequencing data, capturing 16 time points during the differentiation of iPSCs to cardiomyocytes, in 19 human cell lines. They identified hundreds of dynamic expression quantitative trait loci that changed over time, with enrichment in enhancers of relevant cell types. [Science] Abstract | Press Release

(Ranked by impact factor of the journal)

Engineered Signaling Centers for the Spatially Controlled Patterning of Human Pluripotent Stem Cells

The authors present a microfluidic approach that exposed human (h)PSC colonies to spatiotemporally controlled morphogen gradients generated from artificial signaling centers. In response to a localized source of bone morphogenetic protein 4, hPSC colonies reproducibly broke their intrinsic radial symmetry to produce distinct, axially arranged differentiation domains. [Nat Methods] Abstract | Press Release

Transcriptional Dynamics of Pluripotent Stem Cell-Derived Endothelial Cell Differentiation Revealed by Single-Cell RNA Sequencing

A highly efficient directed eight-day differentiation protocol was used to generate a human (h)ESC-derived endothelial cell product, in which 66% of cells co-expressed CD31 and CD144. Investigators observed largely homogeneous hESC and mesodermal populations at days zero and four, respectively, followed by a rapid emergence of distinct endothelial and mesenchymal populations. [Eur Heart J] Full Article

A 3D Model of a Human Epiblast Reveals BMP4-Driven Symmetry Breaking

Researchers used human ESCs to generate an in vitro three-dimensional model of a human epiblast whose size, cell polarity and gene expression were similar to a day ten human epiblast. A defined dose of BMP4 spontaneously broke axial symmetry, and induced markers of the primitive streak and epithelial-to-mesenchymal transition. [Nat Cell Biol] Abstract | Press Release

A High-Throughput Screening and Computation Platform for Identifying Synthetic Promoters with Enhanced Cell-State Specificity (SPECS)

Scientists demonstrated the identification of multiple SPECS that exhibited distinct spatiotemporal activity during the programmed differentiation of iPSCs, as well as SPECS for breast cancer and glioblastoma stem-like cells. [Nat Commun] Full Article

Enhancer Accessibility and CTCF Occupancy Underlie Asymmetric TAD Architecture and Cell Type Specific Genome Topology

The authors explored quantitative aspects of topologically associated domains (TAD) between pluripotent ESC and lineage-committed cells. ESCs exhibited permissive topological configurations which manifested themselves as increased inter- TAD interactions, weaker intra-TAD interactions, and a unique intra-TAD connectivity whereby one border made pervasive interactions throughout the domain. [Nat Commun] Full Article

In Vivo Developmental Trajectories of Human Podocyte Inform In Vitro Differentiation of Pluripotent Stem Cell-Derived Podocytes

To characterize podocyte development, scRNA-seq was performed on human fetal kidneys, identifying distinct transcriptional signatures accompanying the differentiation of functional podocytes from progenitors. Organoid-generated podocytes exhibited highly similar, progressive transcriptional profiles despite an absence of the vasculature, although abnormal gene expression was pinpointed in late podocytes. [Dev Cell] Full Article

Chemically Defined Media Can Maintain Pig Pluripotency Network In Vitro

Investigators report that FGF2, ACTVIN, and WNT signaling were essential to sustain pig pluripotency in vitro. Newly derived pig ESCs were stably maintained over an extended period, and capable of forming teratomas that contained three germ layers. [Stem Cell Reports] Full Article | Graphical Abstract

A Subset of Topologically Associating Domains Fold into Mesoscale Core-Periphery Networks

The authors analyzed high-resolution Hi-C data with graph theory to understand possible mesoscale network architecture within chromatin domains. They identified a subset of topologically associating domains exhibiting strong core-periphery mesoscale structure in ESCs, neural progenitor cells, and cortical neurons. [Sci Rep] Full Article

FGF Family Members Differentially Regulate Maturation and Proliferation of Stem Cell-Derived Astrocytes

Researchers examined the specificity and mechanism of action of fibroblast growth factor (FGF)2 and other FGF family members, as well as neurotrophic and differentiation factors, on mouse ESC-derived astrocytes. They found that some FGFs – including FGF2, strongly increased glutamate transporter 1 expression and enhanced astrocyte proliferation, while others (FGF16 and FGF18) mainly affected maturation. [Sci Rep] Full Article

Improved Osteogenic Differentiation of Human Induced Pluripotent Stem Cells Cultured on Polyvinylidene Fluoride/Collagen/Platelet-Rich Plasma Composite Nanofibers

Scientists investigated the combined effect of nanofibrous scaffolds in combination with platelet-rich plasma (PRP) on the osteogenic differentiation potential of human iPSCs. Electrospinning was used for fabricating nanofibrous scaffolds by polyvinylidene fluoride/collagen with and without PRP. [J Cell Physiol] Abstract

A Mass Spectrometry Survey of Chromatin-Associated Proteins in Pluripotency and Early Lineage Commitment

Investigators used proteomic profiling of the chromatin landscape by chromatin enrichment for proteomics in mouse naive pluripotent ESCs, primed pluripotent epiblast stem cells and cells in early stages of differentiation. They provided a comprehensive overview of epigenetic protein complexes associated with the chromatin and identified proteins associated with the maintenance and loss of pluripotency. [Proteomics] Abstract | Full Article

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Recent Advances of Induced Pluripotent Stem Cells Application in Neurodegenerative Diseases

iPSCs are adult cells that maintain the characteristics of ESCs because it can be genetically reprogrammed to an ESC-like state via express genes and transcription factors. Such cells provide an efficient pathway to explorehuman diseases and their corresponding therapy, particularly neurodevelopmental disorders. [Prog Neuropsychopharmacol Biol Psychiatry] Abstract

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

Semma Therapeutics Announces Pre-Clinical Proof-of-Concept in Two Lead Programs in Type 1 Diabetes

Semma Therapeutics, Inc. announced the achievement of pre-clinical proof-of-concept based on data from its two lead programs for type 1 diabetes testing stem cell-derived islets in both non-human primates and pigs. [Press release from Semma Therapeutics, Inc. discussing research presented at International Society for Stem Cell Research (ISSCR) Annual Meeting 2019, Los Angeles] Press Release

Hemostemix Announces Ongoing Phase II CLI Trial Abstract Accepted for Presentation

Hemostemix Inc. announced that its abstract was accepted at an upcoming meeting. The abstract is entitled “Autologous Stem Cell Treatment for CLI Patients with No Revascularization Options: An Update of the Hemostemix ACP-01 Trial With 4.5 Year Followup” by lead investigator Dr. York Hsiang, Professor of Vascular Surgery, University of British Columbia. [Press release from Hemostemix Inc. discussing research to be presented at the upcoming 41^st Annual Canadian Society for Vascular Surgery Meeting (CSVS), Kelowna] Press Release

Century Therapeutics Launches with USD 250M Financing for Induced Pluripotent Stem Cell (iPSC) Allogeneic Cell Therapy Platform

Century Therapeutics emerged from stealth mode today with USD $250 million in financing commitments from Bayer, Versant and Fujifilm Cellular Dynamics Inc. The proceeds will enable Century to advance multiple programs into the clinic for hematologic and solid malignancies. [Bayer AG] Press Release

Therapeutic Solutions International Obtains Exclusive License for Patented Clinical Stage Adult Stem Cell for Treatment of Military and Sports Brain Injuries

Therapeutics Solutions International, Inc. announced recently signing of the license agreement providing exclusive rights to a patented adult stem cell for development of therapeutics in the area of chronic traumatic encephalopathy and traumatic brain injury. [Therapeutics Solutions International, Inc. (GlobeNewswire, Inc.)] Press Release

University Releases Reports from Investigation of Prominent Geneticist

On July 1^st, University College London released reports from misconduct investigations into the lab of David Latchman, who was a prominent geneticist at the university and is now head of Birkbeck, University of London. The documents describe evidence of research fraud in Latchman’s research group from separate investigations conducted in 2014, 2015, and 2016. [The Scientist] Editorial

Why India Is Striking Back against Predatory Journals

According to 2015 estimates, more than 8,000 predatory journals churn out more than 400,000 items a year, and India — which has also seen a spurt in high-quality scientific publications – contributes more than one-third of the articles in predatory publications. Last month, India launched its latest salvo against the ‘pay and publish trash’ culture that sustains predatory journals. [Nature News] Editorial

NEW Latin American Society for Developmental Biology
October 28-31, 2019
Buenos Aires, Argentina

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

NEW Senior Scientist – Cell Engineering and Characterization (Merck & Co., Inc)

NEW Associate Professor – Developmental and Stem Cell Biology (The University of Hong Kong)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

Postdoctoral Researchers – Molecular Embryology and Biology (Cambridge Stem Cell Institute)

Postdoctoral Fellows – Striated Muscle Regeneration (Duke University)

Postdoctoral Fellow – iPSC Models of Diabetes (New York Stem Cell Foundation)

Postdoctoral Researcher – Cystic Fibrosis Stem Cell Models (The University of Alabama at Birmingham)

Postdoctoral Associate – RNA Genomics in iPSCs (The Jackson Laboratory)

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

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

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

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

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