ESC & iPSC News Volume 15.00 | Jan 8 2020

TOP STORY

Multipotent RAG1⁺ Progenitors Emerge Directly from Hemogenic Endothelium in Human Pluripotent Stem Cell-Derived Hematopoietic Organoids

Under conditions favouring T-cell development, RAG1⁺ cells progressively upregulated a cohort of recognized T-cell-associated genes, arresting development at the CD4⁺CD8⁺ stage. Sort and re-culture experiments showed that early RAG1⁺ cells also possessed B-cell, myeloid and erythroid potential. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

Generating Ring-Shaped Engineered Heart Tissues from Ventricular and Atrial Human Pluripotent Stem Cell-Derived Cardiomyocytes

Researchers showed that engineered heart tissues (EHTs) could be generated by directing human PSCs to differentiate into ventricular or atrial cardiomyocytes, and then embedding these cardiomyocytes in a collagen-hydrogel to create chamber-specific, ring-shaped, EHTs. [Nat Commun] Full Article

SETDB1-Mediated Cell Fate Transition between 2C-Like and Pluripotent States

Investigators found that under the “ground state” of pluripotency with two inhibitors of the MEK and GSK3 pathways, Setdb1-knockout failed to induce trophectoderm (TE) differentiation as in serum/LIF, indicating that TE fate restriction was not the direct target of SETDB1. [Cell Rep] Full Article | Graphical Abstract

Hypothalamic Contribution to Pituitary Functions Is Recapitulated In Vitro Using 3D-Cultured Human iPS Cells

A functional hypothalamic-pituitary unit was generated using human iPS cells in vitro. The adrenocorticotropic hormone secretion capacity of the induced pituitary reached a comparable level to that of adult mouse pituitary because of the simultaneous maturation with hypothalamic neurons within the same aggregates. [Cell Rep] Full Article | Graphical Abstract

T Cell-Derived iPSCs as a Source of Regenerated T Cells: High Frequency Production of iPSC Clones Capable of Generating Potent Cytotoxic T Cells

Investigators developed a method by which cytotoxic T lymphocytes (CTLs) were regenerated from iPSCs that were originally derived from T cells (T-iPSCs). In order to assess the feasibility of this strategy, they investigated the frequency of usable T-iPSC clones in terms of their T cell generating capability and TCR affinity. [Mol Ther Methods Clin Dev] Abstract

Recurrent Genetic Abnormalities in Human Pluripotent Stem Cells: Definition and Routine Detection in Culture Supernatant by Targeted Droplet Digital PCR

Researchers first carried out a large meta-analysis of all human PSC (hPSC) genetic abnormalities reported in more than 100 publications and identified 738 recurrent genetic abnormalities. They then developed a test based on the droplet digital PCR technology that could potentially detect more than 90% of these hPSC recurrent genetic abnormalities in DNA extracted from culture supernatant samples. [Stem Cell Reports] Full Article | Graphical Abstract

A Stem Cell Reporter for Investigating Pluripotency and Self-Renewal in the Rat

Scientists describe an EGFP reporter transgene that tracked expression of the benchmark naive pluripotency marker gene Rex1 (Zfp42) in the rat. Insertion of the EGFP reporter gene downstream of the Rex1 promoter disrupted Rex1 expression, but REX1-deficient rat ESCs and rats were viable and apparently normal, validating this targeted knockin transgene as a neutral reporter. [Stem Cell Reports] Full Article

In Vivo Monitoring of Remnant Undifferentiated Neural Cells following Human iPS Cell-Derived Neural Stem/Progenitor Cells Transplantation

The authors hypothesized that translocator protein (TSPO) would be present in human-iPSC-derived neural stem/progenitor cells (hiPSC-NS/PCs) and expressed strongly in residual immature neural cells after transplantation. They showed high levels of TSPO expression in immature hiPSC-NS/PCs-derived cells, and decreased TSPO expression as neural differentiation progressed in vitro. [Stem Cells Transl Med] Full Article

Embryonic Stem Cell-Derived Extracellular Vesicle-Mimetic Nanovesicles Rescue Erectile Function by Enhancing Penile Neurovascular Regeneration in the Streptozotocin-Induced Diabetic Mouse

Researchers demonstrated in diabetic mice that ESC-derived extracellular vesicle-mimetic nanovesicles completely restored erectile function through enhanced penile angiogenesis and neural regeneration in vivo, whereas ESC partially restored erectile function. [Sci Rep] Full Article

Transplantation of iPS-Derived Vascular Endothelial Cells Improves White Matter Ischemic Damage

Fourteen days after iPSC-derived vascular endothelial cell transplantation, the infarct area remarkably decreased as compared to that just before the transplantation when evaluated by magnetic resonance imaging or luxol fast blue staining, and remyelination was promoted dramatically in the infarct when assessed by luxol fast blue staining. [J Neurochem] Abstract

Biphasic Role of Tgf-β Signaling during Müller Glia Reprogramming and Retina Regeneration in Zebrafish.

Tgf-β signaling not only performed a pro-proliferative function but also was necessary for the expression of several regeneration-associated, essential transcription factor genes such as ascl1a, lin28a, oct4, sox2, zebs, and various microRNAs namely, miR-200a, miR-200b, miR-143 and miR-145 during different phases of retina regeneration. [iScience] Abstract | Graphical Abstract

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Organoid and Pluripotent Stem Cells in Parkinson’s Disease Modeling: An Expert View on Their Value to Drug Discovery

Scientists highlight the generation of iPSC neurons and neural organoids as models for studying Parkinson’s disease. They further discuss the recent work using patient-derived neurons from both familial and sporadic forms of Parkinson’s to study disease pathogenic phenotypes and pathways. [Expert Opin Drug Discov] Abstract

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

Kadimastem Announces Promising Results of Cohort A of its Phase I/IIa Clinical Trial in ALS

Kadimastem Ltd. announced promising results of cohort A of its Phase I/IIa clinical trial for the treatment of patients with amyotrophic lateral sclerosis (ALS). [Kadimastem Ltd.] Press Release

Lineage Provides Update on Patient Enrollment in Phase I/IIa Clinical Study of OpRegen^® for the Treatment of Dry Age-Related Macular Degeneration

Lineage Cell Therapeutics, Inc. announced additional patient data from its ongoing Phase I/IIa clinical study of OpRegen^® the company’s retinal pigment epithelium transplant therapy, for the treatment of dry age-related macular degeneration. [Lineage Cell Therapeutics, Inc.] Press Release

Government Call for Science ‘Weirdos’ Prompts Caution from Researchers

Researchers have reacted with surprise and caution to a bizarrely worded job advertisement posted by a senior UK government adviser. The notice calls for scientists, mathematicians and “super-talented weirdos” to work for the prime minister and to help make “rapid progress with long-term problems”, and cites several scientific papers. [Nature News] Editorial

UK Group Tackles Reproducibility in Research

Last month, 10 UK universities became part of the UK Reproducibility Network, joining a network that already includes stakeholders such as the Academy of Medical Sciences, Research Libraries UK, the National Institute for Biological Standards and Control, journals including Nature and PLOS, and local networks of researchers. [The Scientist] Editorial

NEW Molecular Machines: From Biophysics to Physiology to Disease
July 12-17, 2020
West Dover, Vermont, United States

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

NEW Postdoctoral Training Fellow – Drosophila Genetics (The Francis Crick Institute)

NEW Postdoctoral Fellow – Stem Cell Research (Georgetown University Medical Center)

NEW Postdoctoral Research Fellow – Endocrinology (Cedars-Sinai Medical Center)

NEW Research Associate – Neurological Diseases (University of Cambridge)

Scientist – Stem Cell Biology (Genentech, Inc.)

Postdoctoral Fellowship – Organ Progenitor Fate (University of Copenhagen)

Postdoctoral Fellow Positions – Cardiac iPSCs (Stanford Cardiovascular Institute)

Postdoctoral Fellow – iPSC Heart Cells (Stanford University)

Research Techician – iPSC Culture Lab (University of Luxembourg)

Assistant Specialist – Division of Cardiovascular Medicine (University of California, Davis)

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