ESC & iPSC News Volume 13.44 | Nov 7 2018

TOP STORY

BMI1 Enables Interspecies Chimerism with Human Pluripotent Stem Cells

Researchers showed that the conventional human PSCs (hPSCs) undergo rapid apoptosis when injected into mouse pre-implantation embryos. Forced-expression of BMI1, a polycomb factor in hPSCs overcame the apoptosis and enabled hPSCs to integrate into mouse pre-implantation embryos and subsequently contribute to chimeras with both embryonic and extra-embryonic tissues. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

NuRD-Interacting Protein ZFP296 Regulates Genome-Wide NuRD Localization and Differentiation of Mouse Embryonic Stem Cells

Scientists identified ZFP296 as an ESC-specific nucleosome remodeling and deacetylase (NuRD) interactor that also interacts with the SIN3A complex. Zfp296 knockout ESCs exhibited delayed induction of lineage-specific markers upon differentiation to embryoid bodies. [Nat Commun] Full Article

Oncogenic Role of SFRP2 in p53-Mutant Osteosarcoma Development via Autocrine and Paracrine Mechanism

Using iPSCs generated from Li-Fraumeni syndrome patients, the authors investigated an oncogenic role of secreted frizzled-related protein 2 (SFRP2) in p53 mutation-associated osteosarcoma (OS) development. They found that high SFRP2 expression in OS patient samples correlated with poor survival. [Proc Natl Acad Sci USA] Abstract

Silencing of Retrotransposon-Derived Imprinted Gene RTL1 Is the Main Cause for Postimplantational Failures in Mammalian Cloning

Investigators performed methylome and transcriptome analyses of pig iPSCs and associated cloned embryos, and revealed that aberrant silencing of imprinted genes, in particular the retrotransposon-derived RTL1 gene, is the principal epigenetic cause of pregnancy failure. Restoration of RTL1 expression in pig iPSCs rescued fetal loss. [Proc Natl Acad Sci USA] Full Article

KDM6A and KDM6B Play Contrasting Roles in Nuclear Transfer Embryos Revealed by MERVL Reporter System

Overexpression of the H3K27me3-specific demethylase KDM6A, but not of KDM6B, improved the efficiency of somatic cell nuclear transfer (SCNT). Knockdown of KDM6B increased the rate of SCNT-derived ESCs from Duchenne muscular dystrophy embryos. [EMBO Rep] Full Article

Selective Laminin-Directed Differentiation of Human Induced Pluripotent Stem Cells into Distinct Ocular Lineages

Researchers showed that different isoforms of laminin led to the selective differentiation of human iPSCs (hiPSCs) into different eye-like tissues. The 211 isoform of the E8 fragment of laminin enabled generation of dense hiPSC colonies due to actomyosin contraction, which in turn led to cell density-dependent YAP inactivation and subsequent retinal differentiation in colony centers. [Cell Rep] Full Article | Graphical Abstract

A Screen Using iPSC-Derived Hepatocytes Reveals NAD⁺ as a Potential Treatment for mtDNA Depletion Syndrome

Scientists generated DGUOK-deficient hepatocyte-like cells using iPSCs and used them to identify drugs that could improve mitochondrial ATP production and mitochondrial function. Nicotinamide adenine dinucleotide (NAD) was found to improve mitochondrial function in DGUOK-deficient hepatocyte-like cells by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha. [Cell Rep] Full Article | Graphical Abstract

Step-Wise Chondrogenesis of Human Induced Pluripotent Stem Cells and Purification via a Reporter Allele Generated by CRISPR-Cas9 Genome Editing

Investigators demonstrated cartilaginous matrix production in three unique human iPSC (hiPSC) lines using a robust and reproducible differentiation protocol. To purify chondroprogenitors produced by this protocol, they engineered a COL2A1-GFP knock-in reporter hiPSC line by CRISPR-Cas9 genome editing. [Stem Cells] Abstract | Editorial

SMAD4 Is Essential for Human Cardiac Mesodermal Precursor Cell Formation

Researchers showed that the loss of SMAD4 had no effect on human ESC self-renewal, or neuroectoderm formation, but was essential for the formation of cardiac mesoderm, with a subsequent complete loss of cardiomyocyte formation during human ES cell cardiogenesis. [Stem Cells] Abstract

Synthetic mRNAs Drive Highly Efficient iPS Cell Differentiation to Dopaminergic Neurons

The authors used synthetic mRNAs coding two proneural transcription factors to differentiate iPSCs into midbrain dopaminergic neurons. mRNAs coding Atoh1 and Ngn2 with defined phosphosite modifications led to higher and more stable protein expression, and induced more efficient neuron conversion, as compared to mRNAs coding wild-type proteins. [Stem Cells Transl Med] Full Article

VGF Nerve Growth Factor Inducible Is Involved in Retinal Ganglion Cells Death Induced by Optic Nerve Crush

AQEE-30, a VGF nerve growth factor inducible (VGF) peptide, suppressed the loss of retinal ganglion cells (RGCs) induced by the optic nerve crush, and it increased survival rat-derived RGCs and promoted the outgrowth of neurites of rat and human iPSCs derived RGCs in vitro. [Sci Rep] Full Article

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Systems-Wide Approaches in Induced Pluripotent Stem Cell Models

Combined with advances in various omics technologies, iPSC models can be used to profile the expression of genes, transcripts, proteins, and metabolites in relevant tissues. The authors review recent developments in omics profiling of various molecular phenotypes and the emergence of human iPSCs as a systems biology model of human diseases. [Annu Rev Pathol] Abstract

Modeling Sporadic Alzheimer’s Disease Using Induced Pluripotent Stem Cells

Investigators compare the data obtained from familial Alzheimer’s disease (AD) and sporadic AD (sAD) iPSC-derived cell lines, identify the inconsistencies that exist in sAD models and highlight the potential role of Aβ clearance mechanisms, a relatively under-investigated area in iPSC-derived models, in the study of AD. [Neurochem Res] Full Article

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

Results of Cynata’s World-First GvHD Clinical Trial Accepted for Presentation

Cynata Therapeutics Limited announced that results from Cohort A of the Phase I clinical trial of CYP-001 for the treatment of steroid-resistant acute graft versus host disease (GvHD) will be presented in a poster. The Phase I trial of CYP-001 represents the first time a clinical trial using iPSC-derived MSCs has been completed. [Press release from Cynata Therapeutics Limited (GlobeNewswire, Inc.) discussing research to be presented at the American Society of Hematology (ASH) Annual Meeting, San Diego] Press Release

Asterias Biotherapeutics Announces Positive Outcome from Data Review from OPC1 Spinal Cord Injury Study

Asterias Biotherapeutics, Inc. announced a positive outcome from an independent Data Review Panel’s review of the data generated by patients enrolled in the company’s ongoing Phase I/IIa SCiStar study designed to evaluate the safety and efficacy of OPC1 in the treatment of severe cervical spinal cord injury. [Asterias Biotherapeutics] Press Release

ERS Genomics Licenses CRISPR Gene Editing Technology to DefiniGEN to Develop Human Cell Models to Support the Preclinical Development of Therapeutics

ERS Genomics Limited and DefiniGEN Ltd announced a license agreement to provide DefiniGEN with access to ERS Genomic’s CRISPR/Cas9 genome editing technology patents. DefiniGEN will combine their best-in-class iPSC differentiation platform with CRISPR/Cas9 technology to generate a range of innovative preclinical human models. [ERS Genomics] Press Release

Investigator at CHLA Awarded $1.3 Million to Study Stem Cell Therapy for Liver Failure

Currently, the only therapy for metabolic liver disease is an organ transplant. Tracy Grikscheit, MD, an attending physician and regenerative medicine scientist at Children’s Hospital Los Angeles (CHLA), hopes to change that reality. She has been awarded nearly $1.3 million by the California Institute of Regenerative Medicine to study stem cell therapy for liver failure. [Children’s Hospital Los Angeles (EurekAlert!)] Press Release

Trans-Pacific Institutional Agreement Fosters Close Research Partnership – Hong Kong Polytechnic University and University of Waterloo Sign Historic Institutional Agreement and Plan to Collaborate on World-Class Ocular Research

The Presidents of The Hong Kong Polytechnic University and The University of Waterloo signed a Strategic University Partnership institutional agreement with the objective to foster closer partnership in education, research and entrepreneurship. [The Hong Kong Polytechnic University] Press Release

Some Takeaways for Science from Yesterday’s U.S. Elections

For scientists, the new Democratic majority in the U.S. House of Representatives isn’t the only important result from the midterm election. Four House incumbents active on science issues have been defeated, and a fifth is trailing. [ScienceInsider] Editorial

Two Big Funders Join Open-Access Movement

The Bill & Melinda Gates Foundation and the Wellcome Trust announced that they are endorsing Plan S, an open-access publishing initiative, which means that they will require research they fund to be free to read upon publication, Science reports. [The Scientist] Editorial

NEW Keystone Symposia: Genome Engineering: From Mechanisms to Therapies
February 19-23, 2019
Victoria, British Columbia, Canada

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

NEW Research Fellow – Molecular Phenotypes in Human iPSCs & Derived Neural Cell Types (University College London)

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

Postdoctoral Fellow – Patient Derived Organoids (Rutgers Cancer Institute of New Jersey)

Postdoctoral Position – Gene Modification in HSCs (University of Wisconsin-Madison)

Staff Scientist – Mouse Genome Engineering (Wellcome Sanger Institute)

Postdoctoral Position – Stem Cells and Diabetes (A*STAR)

Postdoctoral Fellows – iPSCs & Blood Development (University of Washington)

Postdoctoral Research Scientist – Precision Medicine (Columbia University)

Postdoctoral Fellow – Stem Cells, Development & Cancer (Albert Einstein College of Medicine)

Director – Center for Cell Reprogramming (Georgetown University)

Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University)

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