ESC & iPSC News Volume 14.14 | Apr 17 2019

TOP STORY

A Compendium of Mutational Signatures of Environmental Agents

Investigators examined mutational signatures in 324 whole-genome-sequencing human-induced pluripotent stem cells exposed to 79 known or suspected environmental carcinogens. Forty-one yielded characteristic substitution mutational signatures. Some were similar to signatures found in human tumors. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Human Pluripotency Is Initiated and Preserved by a Unique Subset of Founder Cells

Researchers identified human pluripotent founder cells (PFCs) that initiate, as well as preserve and establish, PSC cultures. PFCs were marked by N-cadherin expression and reside exclusively at the colony boundary of primate PSCs. [Cell] Abstract | Press Release | Graphical Abstract

Dissecting the Role of H3K27 Acetylation and Methylation in PRC2 Mediated Control of Cellular Identity

The authors presented engineered mouse ESCs targeting the PRC2 subunits EZH1 and EZH2 to discriminate between contributions of distinct H3K27 methylation states and the presence of PRC2/1 at chromatin. They generated catalytically inactive EZH2 mutant ESCs, demonstrating that H3K27 methylation, but not recruitment to the chromatin, was essential for proper ESC differentiation. [Nat Commun] Full Article

MKL1-Actin Pathway Restricts Chromatin Accessibility and Prevents Mature Pluripotency Activation

Scientists reported that MKL1, the key transcriptional co-activator of many actin cytoskeletal genes, regulated genomic accessibility and cell fate reprogramming. The MKL1-actin pathway weakened during somatic cell reprogramming by pluripotency transcription factors. [Nat Commun] Full Article

Transient Activation of the UPR^ER Is an Essential Step in the Acquisition of Pluripotency during Reprogramming

Investigators found that the unfolded protein response of the endoplasmic reticulum (UPR^ER), the mitochondrial UPR, and the heat shock response, which ensured proteome quality during stress, were activated during reprogramming. The UPR^ER was particularly crucial, and its ectopic, transient activation, genetically or pharmacologically, enhanced reprogramming. [Sci Adv] Full Article

Single-Cell RNA-Sequencing-Based CRISPRi Screening Resolves Molecular Drivers of Early Human Endoderm Development

The authors interrogated dynamics in chromatin accessibility during differentiation of ESCs to definitive endoderm (END), predicting DNA-binding proteins that may drive this cell fate transition. They then combined single-cell RNA-seq with parallel CRISPR perturbations to comprehensively define the loss-of-function phenotype of those factors in END development. [Cell Rep] Full Article | Graphical Abstract

Large Scale Generation and Characterization of Homogeneous Populations of Migratory Cortical Interneurons from Human Pluripotent Stem Cells

By employing spinner culture, researchers could obtain a >10fold higher yield of cortical interneuron (cIN) progenitors compared to conventional culture without affecting their phenotype. Generated cIN spheres could be maintained feeder-free up to 10 months and were optimized for passaging and cryopreservation. [Mol Ther Methods Clin Dev] Abstract | Full Article

Transcriptome and Proteome Profiling of Neural Induced Pluripotent Stem Cells from Individuals with Down Syndrome Disclose Dynamic Dysregulations of Key Pathways and Cellular Functions

Scientists established a model using iPSCs with transcriptome profiles comparable to that of normal fetal brain development. When applied on iPSCs with T21, transcriptome and proteome signatures at two stages of differentiation revealed strong temporal dynamics of dysregulated genes, proteins and pathways belonging to 11 major functional clusters. [Mol Neurobiol] Full Article

Assembly of Human Stem Cell-Derived Cortical Spheroids and Vascular Spheroids to Model 3-D Brain-Like Tissues

Hybrid neurovascular spheroids were constructed by fusion of human iPSC-derived cortical neural progenitor cell (iNPC) spheroids, endothelial cell (iEC) spheroids, and the supporting human mesenchymal stem cells (MSCs). Single hybrid spheroids were constructed at different iNPC: iEC: MSC ratios. The incorporation of MSCs upregulated the secretion levels of cytokines VEGF-A, PGE2, and TGF-β1 in hybrid spheroid system. [Sci Rep] Full Article

A Novel Approach to Differentiate Rat Embryonic Stem Cells In Vitro Reveals a Role for RNF12 in Activation of X Chromosome Inactivation

Researchers adapted existing protocols to establish a novel monolayer differentiation protocol for rat ESCs to study X chromosome inactivation. They showed that differentiating rat ESCs properly downregulated pluripotency factor genes, and presented female specific Xist RNA accumulation and silencing of X-linked genes. [Sci Rep] Full Article

Screening of Pure Synthetic Coating Substrates for Induced Pluripotent Stem Cells and iPSC-Derived Neuroepithelial Progenitors with Short Peptide Based Integrin Array

A commercially available integrin array established by synthetic integrin binding peptides was used to screen coating substrates for iPSCs and NEPs. The authors showed that binding peptides of integrin α5β1, αVβ1, αMβ2 and αIIbβ3 supported cell adhesion of iPSCs, while α5β1, αVβ1 and αIIbβ3 binding peptides supported NEPs adhesion. [Exp Cell Res] Abstract

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APC/C Ubiquitin Ligase: Coupling Cellular Differentiation to G1/G0 Phase in Multicellular Systems

The author reviews recent advances in the function of APC/C in animal development, specifically focusing on its emerging role in regulating cell differentiation. They describe how APC/C regulates distinct processes during the course of differentiation by deploying diverse molecular machineries in a variety of developmental contexts. [Trends Cell Biol] Abstract

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

BioTime to Present Data from OpRegen^® Phase I/IIa Clinical Study

BioTime, Inc. announced that updated results from a Phase I/IIa clinical study of its lead product candidate, OpRegen^®, a retinal pigment epithelium cell transplant therapy currently in development for the treatment of dry age-related macular degeneration with geographic atrophy, will be presented. [Press release from BioTime, Inc. discussing research to be presented at the 2019 Association for Research in Vision and Ophthalmology Annual Meeting (ARVO 2019), Vancouver] Press Release

Allele Biotechnology and SCM Lifescience Sign a Joint Research and Development Agreement to Develop iPSC-Based Diabetes Treatment

Allele Biotechnology and Pharmaceuticals, Inc. officially announced a joint research and development agreement with SCM Lifescience Co., Ltd., for the development of diabetes therapies using pancreatic beta cells derived from iPSCs. [Allele Biotechnology and Pharmaceuticals, Inc. (Business Wire, Inc.)] Press Release

ACEA Biosciences – a Part of Agilent Launches the xCELLigence RTCA ePacer to Improve the Quality and Functionality of hiPSC-Cardiomyocytes for Drug Discovery, Safety Pharmacology, and Cardiac Disease Research

ACEA Biosciences – A Part of Agilent unveiled the new xCELLigence^® RTCA ePacer™ during their workshop held at the Society of Toxicology (SOT) Annual Meeting in Baltimore. Human iPSC cardiomyocytes are increasingly being used as a human-relevant in vitro model system for drug discovery, safety pharmacology, and cardiac disease research. [ACEA BIO (Business Wire, Inc.)] Press Release

‘Friendly’ Reviewers Rate Grant Applications More Highly

Peer reviewers are four times more likely to give a grant application an “excellent” or “outstanding” score rather than a “poor” or “good” one when they are chosen by the grant’s applicants, an analysis of Swiss funding applications has found. [Nature News] Editorial

Indian Scientists Launch Preprint Repository to Boost Research Quality

Researchers in India will soon have their own preprint repository where they can post manuscripts from any discipline. The founders of IndiaRxiv hope it will improve the quality of science in the country. [Nature News] Editorial

Stanford Clears Three Faculty Members of ‘CRISPR Babies’ Involvement

Stanford University cleared three faculty members of any misconduct in their interactions with the Chinese scientist who created “CRISPR babies” last year. [STAT News] Editorial

NEW Germ Cell Programming in Vertebrate Biology, Medicine and Biotechnology
May 19-24, 2019
Hong Kong, China

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

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

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

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

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

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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