ESC & iPSC News Volume 13.18 | May 9 2018

TOP STORY

NOTCH Signaling Specifies Arterial-Type Definitive Hemogenic Endothelium from Human Pluripotent Stem Cells

Using a chemically defined human PSC (hPSC) differentiation system combined with the use of DLL1-Fc and DAPT to manipulate NOTCH, investigators discovered that NOTCH activation in hPSC-derived immature hemogenic endothelium (HE) progenitors leads to formation of CD144⁺CD43^–CD73^–DLL4⁺Runx1 + 23-GFP⁺ arterial-type HE, which requires NOTCH signaling to undergo endothelial-to-hematopoietic transition and produce definitive lympho-myeloid and erythroid cells. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

A CRISPR Knockout Screen Identifies SETDB1-Target Retroelement Silencing Factors in Embryonic Stem Cells

Researchers performed a genome-wide CRISPR screen to advance the understanding of retroelement silencing in mouse ESCs. They characterized two factors, MORC2A and DRES1, of which DRES1 is novel molecule in retroelement silencing. Although both factors were recruited to repress provirus, their roles in repression are different. [Genome Res] Abstract

Sin3a-Tet1 Interaction Activates Gene Transcription and Is Required for Embryonic Stem Cell Pluripotency

Scientists report that down-regulation of Sin3a led to the loss of ESC self-renewal and skewed differentiation into mesendoderm lineage. They found that Sin3a functioned as a transcriptional coactivator of the critical Nodal antagonist Lefty1 through interacting with Tet1 to de-methylate the Lefty1 promoter. [Nucleic Acids Res] Full Article

Opposing Roles of miR-294 and MBNL1/2 in Shaping the Gene Regulatory Network of Embryonic Stem Cells

The authors showed that a subset of alternative splicing events in ESCs is dependent on miR‐294 expression. Remarkably, roughly 60% of these splicing events were affected by the depletion of muscleblind‐like splicing regulator 1 and 2 (Mbnl1/2). [EMBO Rep] Abstract | Graphical Abstract

Autologous and Heterologous Cell Therapy for Hemophilia B toward Functional Restoration of Factor IX

Investigators generated iPSCs from two hemophilia B patients and corrected the disease-causing mutations in them by two different approaches (mutation specific and universal). These corrected iPSCs were differentiated into hepatocyte-like cells and transplanted into hemophilic mice. [Cell Rep] Abstract | Press Release | Graphical Abstract

NoRC Recruitment by H2A.X Deposition at rRNA Gene Promoter Limits Embryonic Stem Cell Proliferation

Scientists showed that H2A.X defines the rate of mouse ESC proliferation independently of the DNA damage response pathway, and it associates with three major chromatin-modifying complexes. [Cell Rep] Full Article | Graphical Abstract

Pluripotent Stem Cell Model of Nakajo-Nishimura Syndrome Untangles Proinflammatory Pathways Mediated by Oxidative Stress

To investigate and understand the mechanisms and signal pathways in Nakajo-Nishimura syndrome, researchers established a panel of isogenic PSC lines with PSMB8 mutation. Activity of the immunoproteasome in PSMB8-mutant PSC-derived myeloid cell lines (MLs) was reduced even without stimulation compared with non-mutant-MLs. [Stem Cell Reports] Full Article

Novel Imprinted Single Cpg Sites Found by Global Dna Methylation Analysis in Human Parthenogenetic Induced Pluripotent Stem Cells

In humans, mature cystic ovarian teratomas originate from parthenogenetic activation of oocytes; they are composed of highly differentiated mature tissues containing all three germ layers. To establish human parthenogenetic iPSCs, investigators generated parthenogenetic fibroblasts from ovarian teratoma tissues. [Epigenetics] Abstract

Laser Bioprinting of Human Induced Pluripotent Stem Cells — The Effect of Printing and Biomaterials on Cell Survival, Pluripotency, and Differentiation

Laser bioprinting of undifferentiated human iPSCs (hiPSCs) in combination with different biomaterials was performed and the impact on cells’ behavior, pluripotency, and differentiation was investigated. The findings suggest that hiPSCs are indeed more sensitive to the applied biomaterials, but not to laser printing itself. [Biofabrication] Abstract

Long Non-Coding RNAs Involved in the Regulatory Network During Porcine Pre-Implantation Embryonic Development and iPSC Induction

Using a weighted gene co-expression network analysis, the authors constructed the regulatory network and determined that the novel lncRNAs were functionally involved in key events of embryonic development during the pre-implantation period; moreover, reprogramming could be delineated by a small number of potentially functional modules of co-expressed genes. [Sci Rep] Full Article

VSELs Maintain Their Pluripotency and Competence to Differentiate after Enhanced Ex Vivo Expansion

Scientists found that more than a thousand genes are downregulated in very small embryonic-like stem cells (VSELs), as well as many membrane receptors, cells signaling molecules and cyclin dependent kinases mRNAs. They observed discordance in some pluripotent genes expression levels with ESCs, which could explain VSELs quiescence. [Stem Cell Rev] Full Article

Insights into C9ORF72-Related ALS/FTD from Drosophila and iPSC Models

Approaches that combine the genetic power of Drosophila and the disease relevance of iPSC-derived patient neurons will continue to unravel the underlying pathogenic mechanisms and help identify potential therapeutic targets in C9ORF72-ALS/FTD. [Trends Neurosci] Abstract

Contribution of Induced Pluripotent Stem Cell Technologies to the Understanding of Cellular Phenotypes in Schizophrenia

The authors review the literature and focus on studies that have utilized patient-derived iPSCs to model the pathogenesis of schizophrenia. They also discuss the challenges in modeling cellular phenotypes of schizophrenia. [Neurobiol Dis] Full Article

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

Platelet BioGenesis Licenses Induced Pluripotent Stem Cell Technology from iPS Academia Japan

Platelet BioGenesis announced it has licensed patents related to iPS cells from iPS Academia Japan’s patent portfolio. [Platelet BioGenesis] Press Release

Dr. Robert J. Hariri Honored at Unite to Cure, the 4^th International Vatican Conference, with the 2018 Pontifical Key Innovation Award

Dr. Robert J. Hariri, Founder and CEO of Celularity, has been awarded with the 2018 Pontifical Key Innovation Award by the Vatican’s Pontifical Council for Culture and the Cura Foundation. Dr. Hariri is widely known for his pioneering research in the cell therapy space and is recognized for the discovery of pluripotent stem cells in the placenta. [Celularity (PR Newswire Association LLC.)] Press Release

Dr. James Wells presents his group’s work on hPSC-derived GI organoids and their use for studying disease. Watch Now

Australian Budget Delivers for Science Facilities and Medical Research

The government will push to invest almost Aus$1.9 billion (US$1.4 billion) over the next 12 years in shared research infrastructure — such as microscopes, supercomputers, a marine observing system and telescopes used in myriad disciplines, from nanotechnology to oceanography. Medical research will receive an increase of $1.3 billion, to be spent on various programs and initiatives over 10 years that improve health and boost the medical industry, including $500 million for a genomics and precision-medicine initiative. [Nature News] Editorial

Animal Tests Surge under New U.S. Chemical Safety Law

The cause of the increase isn’t clear. But the new law imposes stricter requirements on a broader array of chemicals than its predecessor, including both new products and ones already on the market, and experts say Environmental Protection Agency staff may be trying to comply by gathering more test data from companies. [ScienceInsider] Editorial

NEW IABS 4^th Cell Therapy Conference: Manufacturing and Testing of Pluripotent Stem Cells
June 5-6, 2018
Los Angeles, California, United States

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

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

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

NEW Postdoctoral Fellow – hiPSC Based Cardiac Regeneration (Duke University)

NEW Postdoctoral Fellow – Human Skeletal Muscle Disease Modeling and Regeneration (Duke University)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

PhD Candidate Position – Cardiovascular Diseases and iPSCs (University Medical Center Göttingen)

Scientist/Senior Scientist – Bioprocess Engineering (Bluerock Therapeutics, LLC.)

Postdoctoral Fellow Positions – Cardiovascular Stem Cell/iPSC Biology (University of Illinois at Chicago)

Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

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

Postdoctoral Fellow – Immunology and iPSCs (Stanford University)

Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University)

Postdoctoral Fellow – Stem Cell Biology (City of Hope)

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