ESC & iPSC News Volume 15.22 | June 10 2020

TOP STORY

Hair-Bearing Human Skin Generated Entirely from Pluripotent Stem Cells

Scientists report an organoid culture system that generated complex skin from human PSCs. They used stepwise modulation of the transforming growth factor β and fibroblast growth factor signaling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. [Nature] Full Article | Press Release

(Ranked by impact factor of the journal)

Reconstruction of the Human Blood-Brain Barrier In Vitro Reveals a Pathogenic Mechanism of APOE4 in Pericytes

Researchers revealed the role of pericytes in apolipoprotein (APOE4)-mediated cerebral amyloid angiopathy (CAA) and highlighted calcineurin-nuclear factor of activated T cells signaling as a therapeutic target in CAA and Alzheimer’s disease. [Nat Med] Full Article

TETs Compete with DNMT3 Activity in Pluripotent Cells at Thousands of Methylated Somatic Enhancers

Investigators analyzed the independent and combined effects of positive DNMT3A/B and negative TET1-3 regulators on the DNA methylation landscape using a panel of knockout human ESC lines. [Nat Genet] Abstract

Alzheimer’s-Associated PLCγ2 Is a Signaling Node Required for Both TREM2 Function and the Inflammatory Response in Human Microglia

The authors used genetically engineered human iPSC-derived microglia-like cells to show that triggering receptor expressed on myeloid cells 2 (TREM2) signaled through PLCγ2 to mediate cell survival, phagocytosis, processing of neuronal debris, and lipid metabolism. [Nat Neurosci] Abstract

Synergistic Gene Editing in Human iPS Cells via Cell Cycle and DNA Repair Modulation

Scientists established a fluorescent DNA repair assay in human iPSCs to visualize and quantify the frequency of DNA repair outcomes during monoallelic and biallelic targeting. [Nat Commun] Full Article

N-3 Polyunsaturated Fatty Acids Promote Astrocyte Differentiation and Neurotrophin Production Independent of cAMP in Patient-Derived Neural Stem Cells

iPSC-derived neuronal stem cell lines were generated from individuals with major depressive disorder. Astrocytes differentiated from patient-derived neuronal stem cells were verified by GFAP and cells were treated with eicosapentaenoic acid, docosahexaenoic acid or stearic acid. [Mol Psychiatry] Abstract

Hippo-Yap Signaling Controls Lineage Differentiation of Mouse Embryonic Stem Cells through Modulating the Formation of Super-Enhancers

Investigators found that knockout of Mst1 and Mst2, two key components of the Hippo signaling in mouse ESCs, resulted in a disruption of differentiation into mesendoderm lineage. They revealed a novel mechanism on how the Hippo-YAP signaling pathway dictated ESC lineage differentiation. [Nucleic Acids Res] Full Article

Acute Myeloid Leukemia iPSCs Reveal a Role for RUNX1 in the Maintenance of Human Leukemia Stem Cells

Researchers report that genetically clonal iPSCs derived from an acute myeloid leukemia patient and characterized by exceptionally high engraftment potential gave rise, upon hematopoietic differentiation, to a phenotypic hierarchy. [Cell Rep] Full Article | Graphical Abstract

Assembly and Function of a Bioengineered Human Liver for Transplantation Generated Solely from Induced Pluripotent Stem Cells

Improving methods for liver decellularization, recellularization, and differentiation of different liver cellular lineages of human iPSCs in an organ-like environment, investigators generated functional engineered human mini-livers and performed transplantation in a rat model. [Cell Rep] Full Article | Graphical Abstract

Pro-Maturational Effects of Human iPSC-Derived Cortical Astrocytes upon iPSC-Derived Cortical Neurons

The authors examined interactions between human astrocytes and neurons derived from a common cortical progenitor pool, thereby recapitulating aspects of in vivo cortical development. They showed that the cortical iPSC-derived astrocytes exhibited many of the molecular and functional hallmarks of astrocytes. [Stem Cell Reports] Full Article | Graphical Abstract

Inhibition of Apoptosis Reduces Diploidization of Haploid Mouse Embryonic Stem Cells during Differentiation

Scientists induced p53-deficient haploid ESCs into multiple differentiated lineages, maintaining haploid status in vitro. Haploid cells also remained in chimeric embryos and teratomas arising from p53-null haploid ESCs. [Stem Cell Reports] Full Article | Graphical Abstract

Energy Metabolism and Mitochondrial Defects in X-Linked Charcot-Marie-Tooth (CMTX6) iPSC-Derived Motor Neurons With the p.R158H PDK3 Mutation

Researchers generated iPSCs by re-programming CMTX6 fibroblasts. They also engineered an isogenic control and demonstrated that genetic correction of the p.R158H mutation reversed the CMTX6 phenotype. [Sci Rep] Full Article

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Prevention of Tumor Risk Associated with the Reprogramming of Human Pluripotent Stem Cells

The authors focus on the risk of tumor formation by human PSCs, and on the possible treatment options if it occurs. Potential new techniques that target epigenetic processes and chromatin regulation provide opportunities for human cancer modeling and regenerative medicine. [J Exp Clin Cancer Res] Full Article

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

International Prize Awarded to Two Pieces of Novel Research in the 3Rs

The 2019 3Rs prize has been jointly awarded to Dr Francesca Nunn and Dr Marta Shahbazi. Marta and colleagues have developed advanced 3D cultures of human and mouse ESCs to mimic the development of the embryo at implantation and the subsequent morphogenesis and formation of the amniotic cavity. [EurekAlert!] Press Release

As Pandemic Pounds US Universities, Federal Support Helps Their Labs Stay Afloat

This spring, as the coronavirus pandemic shuttered US higher education, many college presidents began to warn of the dire financial impact of a frozen US economy on their institutions. Their mix of revenue sources largely determined how much they might be hurt. [ScienceInsider] Editorial

As the Pandemic Hits Campus Finances, Faculty Face Layoffs

The pandemic has bored holes in budgets at universities and colleges across the US and beyond. To stem the spread of the coronavirus, higher education institutions shuttered their campuses, sent students home, and moved classes online. [The Scientist] Editorial

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NEW Postdoctoral Fellow – CRISPR Neurodegenerative Disease Modeling (Wellcome Sanger Institute)

Postdoctoral Researcher (National University of Ireland Galway)

NEW Postdoctoral Position – Cardiovascular Molecular Mechanics (Spanish National Center for Cardiovascular Research)

Scientist – CAR Engineering and Protein Sciences (Century Therapeutics)

Research Scientist – Stem Cells (Evotec SE)

Fellowship Position – Genome Stem Cell Research (Center for Biologics Evaluation and Research)

Postdoctoral Position – Human iPS Models (The Jackson Laboratory)

Postdoctoral Fellow – Bioinformatics of Stem Cell Epigenetics (Albert Einstein College of Medicine)

PhD Candidate – Cardiovascular Diseases (University Medical Center Göttingen)

Senior Scientist – Human iPSC Gene Engineering (Empyrean Therapeutics Ltd)

Postdoctoral Fellow – ALS (Johns Hopkins University School of Medicine)

Research Specialist – Stem Cells for Regenerative Medicine (University of Illinois at Chicago)

Postdoctoral Position – Human Pluripotent Stem Cells to Hepatobiliary Tissues (Johns Hopkins University School of Medicine)

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