ESC & iPSC News Volume 14.26 | Jul 10 2019

TOP STORY

E2F4 Regulates Transcriptional Activation in Mouse Embryonic Stem Cells Independently of the RB Family

Researchers showed that E2F4 was important for the proliferation and the survival of mouse ESCs. In these cells, E2F4 acted in part as a transcriptional activator that promoted the expression of cell cycle genes. This role for E2F4 was independent of the RB family. [Nat Commun] Full Article

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Compression Generated by a 3D Supracellular Actomyosin Cortex Promotes Embryonic Stem Cell Colony Growth and Expression of Nanog and Oct4

Scientists report that colony-growing mouse ESCs (mESCs) generated significant tension on the colony surface through the contraction of a three-dimensional supracellular actomyosin cortex (3D-SAC). Disruption of the 3D-SAC, whose organization was dependent on the Rho/Rho-associated kinase signals and E-cadherin, resulted in mESC colony destruction. [Cell Syst] Full Article | Graphical Abstract

Targeted Genetic Screening in Mice through Haploid Embryonic Stem Cells Identifies Critical Genes in Bone Development

Investigators developed a targeted genetic screening approach in mice through combining androgenetic haploid ESCs (AG-haESCs) and clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR-Cas9) technology. They produced a mutant semi-cloned mice pool by oocyte injection of AG-haESCs carrying constitutively expressed Cas9 and an single guide RNA library targeting 72 preselected genes in one step and screened for bone-development-related genes through skeletal analysis at birth. [PLoS Biol] Full Article

Blockade of STAT3 Causes Severe In Vitro and In Vivo Maturation Defects in Intestinal Organoids Derived from Human Embryonic Stem Cells

The authors found that STAT3 kockout (KO) did not affect the differentiation of human ESCs into human intestinal organoids (hIOs) but rather affected the in vitro maturation of hIOs. STAT3 KO hIOs displayed immature morphologies with decreased size and reduced budding in hIOs even after in vitro maturation. [J Clin Med] Full Article

High-Content Screen in Human Pluripotent Cells Identifies miRNA-Regulated Pathways Controlling Pluripotency and Differentiation

Researchers investigated the effects of 31 miRNAs on NTera-2 and H1 human ESCs, by transfecting miRNA mimics. Following three-four days of culture, cells were stained for the pluripotency marker OCT4 and the G2 cell-cycle marker Cyclin B1, and nuclei and cytoplasm were co-stained with Hoechst and Cell Mask Blue, respectively. [Stem Cell Res Ther] Full Article

MFN2 Silencing Promotes Neural Differentiation of Embryonic Stem Cells via the Akt Signaling Pathway

The authors aimed at revealing the functional role of mitofusin 2 (MFN2) in the pluripotency maintenance and primitive differentiation of ESCs. A dox inducible silencing and routine overexpressing approach was used to downregulate and upregulate MFN2 expression, respectively. They compared the morphology, cell proliferation, and expression level of pluripotent genes in various groups. [J Cell Physiol] Abstract

Engineering a Humanized Telomerase Reverse Transcriptase Gene in Mouse Embryonic Stem Cells

Investigators discovered that the 5′ intergenic region, introns 2 and 6 of human telomerase gene (hTERT) were critical for regulating its promoter in somatic cells. Accordingly, they engineered a humanized gene, hmTert, by knocking-in a 47-kilobase hybrid fragment containing these human non-coding sequences into the mTert locus in mouse ESCs. [Sci Rep] Full Article

Different Effects of Knockouts in ALDH2 and ACSS2 on Embryonic Stem Cell Differentiation

Treatment of wildtype ESCs with acetaldehyde or 4-hydroxynonenal (4-HNE), another substrate of aldehyde dehydrogenase (ALDH2), increased differentiation-associated transcripts compared to levels in untreated cells. mRNAs of genes involved in retinoic acid synthesis were also increased by EtOH, acetaldehyde, and 4-HNE treatment. [Alcohol Clin Exp Res] Abstract

Deletion of Tet Proteins Results in Quantitative Disparities during ESC Differentiation Partially Attributable to Alterations in Gene Expression

Using a combination of transcriptomic and epigenomic approaches scientists demonstrated an increase in DNA hypermethylation and a divergence of transcriptional profiles in pluripotency among Tet deletions, with loss of Tet2 having the most profound effect in undifferentiated ESCs. [BMC Dev Biol] Full Article

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Strategies for Derivation of Endothelial Lineages from Human Stem Cells

The authors discuss a variety of human stem cells, which can be induced to differentiate into endothelial cells (ECs) and review the multifarious approaches for EC generation, such as 3D EB formation for ESCs, stem cell-somatic cell co-culture, and directed endothelial differentiation with growth factors in conventional 2D culture. [Stem Cell Res Ther] Full Article

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

Organovo Presents Data on Creating Stem Cell-Based Bioprinted Kidney Organoids

Organovo Holdings, Inc. presented data on fabricating stem cell-based kidney tissues. Organovo has continued to adapt stem-cell based approaches to developing kidney tissues using its leading 3D bioprinting platform. [Press release from Organovo Holdings, Inc. discussing research presented at the International Society for Stem Cell Research (ISSCR) 2019 Annual Meeting, Los Angeles] Press Release

StemoniX^® Uses microBrain^® Opens New, State-of-the-Art Research & Development Facility

StemoniX^® announced the opening of its new, state-of-the-art research & development facility in La Jolla, CA. The facility will house StemoniX’s research team, who will concentrate on developing new preclinical applications, disease modeling techniques, and drug discovery opportunities involving the company’s high-throughput microOrgan technology platforms. [StemoniX] Press Release

Keeping Do-It-Yourself Gene Science Safe

Two Case Western Reserve University faculty members have received a two-year grant to provide regulatory recommendations for gene-editing research conducted in non-traditional settings. The aim of this $160,000 grant from the National Human Genome Research Institute at the National Institutes of Health is to protect the public while encouraging creativity and innovation that could benefit many people. [Case Western Reserve University] Press Release

As Visa Difficulties Persist, Scientists Push for Change

Individual researchers and science societies are finding solutions so colleagues around the globe can attend conferences, from remote presentations to relocating conferences. [The Scientist] Editorial

Scandal-Weary Swedish Government Takes Over Research-Fraud Investigations

Bruised by a string of high-profile scientific-misconduct cases, Sweden has laid the legislative groundwork for a government agency that will handle all allegations of serious research misconduct. The country follows in the footsteps of neighbouring Denmark, which created the world’s first such agency in 2017. [Nature News] Editorial

Health Canada Orders Halt to Unproven Stem Cell-Based Injection Treatments

Health Canada has launched a crackdown on clinics offering unproven, potentially unsafe treatments that inject a patient with their own cells, ordering three dozen of them to stop offering the services immediately. The clinics, located in BC, Alberta, Ontario and Quebec, advertised a variety of stem cell and platelet-rich plasma treatments for numerous conditions, including heart problems, arthritis, multiple sclerosis, Crohn’s disease, hair loss and skin rejuvenation. [The Globe and Mail] Editorial

NEW 6^th Annual European Congress on Clinical and Translational Medicine
October 18-20, 2019
Vienna, Austria

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

NEW Research Technologist – Pluripotent Stem Cell Biology (STEMCELL Technologies Inc.)

NEW Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

NEW Research Technician – Beta Cell Production from Human PSCs (Helmholtz Zentrum München)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

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

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

Postdoctoral Fellows – Striated Muscle Regeneration (Duke University)

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

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

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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