ESC & iPSC News Volume 13.28 | Jul 18 2018

TOP STORY

Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming

Scientists identified and molecularly characterized rare, early intermediates poised to reprogram with up to 95% efficiency, without perturbing additional genes or pathways, during iPSC generation from mouse embryonic fibroblasts. Analysis of these cells uncovered transcription factors that are important for reprogramming but dispensable for pluripotency maintenance. [Cell Stem Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

GRHL2-Dependent Enhancer Switching Maintains a Pluripotent Stem Cell Transcriptional Subnetwork after Exit from Naive Pluripotency

The authors showed that the transcription factor GRHL2 was necessary and sufficient to activate an epithelial subset of enhancers as naive ESCs transition into formative epiblast-like cells (EpiLCs). Many GRHL2 target genes did not change in expression during the ESC-EpiLC transition. Instead, enhancers regulating these genes in ESCs diminished in activity in EpiLCs while GRHL2-dependent alternative enhancers became activated to maintain transcription. [Cell Stem Cell] Abstract | Graphical Abstract

NKX3-1 Is Required for Induced Pluripotent Stem Cell Reprogramming and Can Replace OCT4 in Mouse and Human iPSC Induction

Following knockdown of NKX3-1, iPSC reprogramming was abrogated. NKX3-1 functioned downstream of the IL-6-STAT3 regulatory network to activate endogenous OCT4. Importantly, NKX3-1 substituted for exogenous OCT4 to reprogram both mouse and human fibroblasts at comparable efficiencies and generated fully pluripotent stem cells. [Nat Cell Biol] Abstract | Press Release

DNMT3A and TET1 Cooperate to Regulate Promoter Epigenetic Landscapes in Mouse Embryonic Stem Cells

Investigators demonstrated that DNA methyltransferase 3A (DNMT3A) and TET1 functioned in a complementary and competitive manner in mouse ESCs to mediate proper epigenetic landscapes and gene expression. The longer isoform of DNMT3A, DNMT3A1, exhibited significant enrichment at distal promoters and canyon edges, but was excluded from proximal promoters and canyons where TET1 showed prominent binding. [Genome Biol] Full Article

Human Induced Pluripotent Stem Cells Generate Light Responsive Retinal Organoids with Variable and Nutrient Dependent Efficiency

Researchers investigated five different human iPSC lines and showed a significant variability in their efficiency to generate retinal organoids. Despite this variability, by month five of differentiation, all iPSC‐derived retinal organoids were able to generate light responses, albeit immature, comparable to the earliest light responses recorded from the neonatal mouse retina, close to the period of eye opening. [Stem Cells] Abstract

An Optimized System for Effective Derivation of Three-Dimensional Retinal Tissue via Wnt Signaling Regulation

By evaluating dickkopf‐related protein 1 (DKK‐1) expression and supplying DKK‐1 if necessary, retinal organoids were differentiated from six human iPSC lines, which were reprogrammed from three common initiating cell types. Retinal tissues derived from the optimized system were well organized and capable of surviving for further maturation. [Stem Cells] Abstract

Effect of Microgravity on Proliferation and Differentiation of Embryonic Stem Cells in an Automated Culturing System during the TZ-1 Space Mission

Space microgravity maintained stemness and long‐term survival of mouse ESCs, promising 3D aggregate formation. Although microgravity did not significantly prevent the migration of embryoid bodies on the ECM substrate, it did prevent terminal differentiation of cells. [Cell Prolif] Abstract

Generation of CD34 Fluorescent Reporter Human Induced Pluripotent Stem Cells for Monitoring Hematopoietic Differentiation

Reporter human iPSCs (hiPSCs) were in vitro differentiated toward CD34⁺ cells using the STEMdiff Hematopoietic Kit combined with short term inhibition of glycogen synthase kinase 3. All cells expressing nuclear green fluorescent protein were positive for cell surface CD34, thus allowing the direct monitoring of the differentiation of hiPSCs into CD34⁺ cells either by flow cytometry or confocal microscopy. [Stem Cells Dev] Abstract

A New Genetic Tool to Improve Immune-Compromised Mouse Models: Derivation and CRISPR/Cas9-Mediated Targeting of NRG Embryonic Stem Cell Lines

Investigators described the derivation of ESC lines from NOD‐Rag1‐il2Rg (NRG) pre‐implantation embryos generated by in vitro fertilization followed by the CRISPR/CAS9 targeting of the Gata‐2 locus. After injection into morula stage embryos, cells from three tested lines gave rise to chimeric adult mice showing high contribution of the ESCs, assessed by coat color. [Genesis] Abstract

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Pluripotent Stem Cell Platforms for Drug Discovery

The authors discuss mechanisms of drug discovery and drug repurposing, and roles of membrane drug transporters in tissue maturation and human PSC-based drug discovery using the example of drugs that target various mutations of CFTR, the cystic fibrosis transmembrane conductance regulator gene, in patients with cystic fibrosis. [Trends Mol Med] Abstract

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

HUB Announces Collaboration with Merck to Develop Organoid Models for Toxicology

The collaboration between Merck and HUB seeks to study intestinal toxicity using adult stem cell derived organoids from different species, including human. HUB organoids are an in vitro cell culture system derived from patients or animals that are genetically and phenotypically stable and faithfully recapitulate characteristics of the tissues from which they were derived. [Hubrecht Organoid Technology] Press Release

Israel Grants $33 Million to GE, Medtronic, Change Healthcare to Boost R&D

Three multinational companies have received an Israeli government grant of 120 million shekels ($33 million) aimed at boosting the presence of large companies and establishing Israel as a hub in biotechnology and medicine. [Reuters] Press Release

Researcher Teams Awarded Nearly $12 Million in CIHR Funding

Seventeen projects across the Research Institute of the McGill University Health Center received a total of $11,888,658 million in project and bridge grant funding. The competition has approved 369 research grants, plus an additional 39 bridge grants for a total investment of approximately $277 million across Canada. [McGill University Health Centre] Press Release

Hungarian Academy President Vows to Keep Fighting for Independence as Government Takes Control

Hungary’s parliament approved an amendment that makes it legally possible to transfer a large part of the budget of the Hungarian Academy of Sciences in Budapest to the country’s newly established Ministry of Innovation and Technology. [ScienceInsider] Editorial

Cancer Geneticist Quits after Harassment Allegations

Following numerous allegations that she harassed fellow employees, Nazneen Rahman, a cancer geneticist at the Institute of Cancer Research in the U.K., will leave her post. Rahman had already been on administrative leave since last November. Dozens of colleagues signed a letter last year describing bullying by Rahman. [The Scientist] Editorial

Questions Raised About “Breakthrough” Therapies’ Clinical Support

The FDAs “breakthrough therapy” designation has helped expedite the development and approval of more than 45 therapeutics in the last 5 years. But a study published in JAMA suggests that these interventions gain FDA approval on the basis of weaker clinical evidence than those that don’t have the breakthrough designation do—a finding that contrasts with public optimism about these drugs’ effectiveness. [The Scientist] Editorial

NEW 2018 Till & McCulloch Meetings (TMM2018)
November 12-14, 2018
Ottawa, Ontario, Canada

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

NEW Postdoctoral Position – Pluripotency, Signaling & Epigenetics (Washington University School of Medicine)

Senior Scientist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

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

Postdoctoral Scholar – Cellular Basis of Morphogenesis (University of California, San Francisco)

Postdoctoral Scholar – Pluripotent Stem Cell Biology (University of California, Berkeley)

Research Associate – Embryonic Stem Cell Derivatives for Vascular Grafts (Imperial College London)

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

Research Associate/Scientist – iPSC Research and Manufacture (Evotec AG)

Postdoctoral Positions – Human Functional Genomics of Aging & Disease (Albert Einstein College of Medicine of Yeshiva University)

Research Associate/PhD Position – iPSCs & Neurodegenerative Disease (TU Dresden)

Research Specialist – Cardiovascular Disease (University of Illinois)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University Feinberg School of Medicine)

Postdoctoral Fellow – hiPSC Based Cardiac Regeneration (Duke University)

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

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

Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University)

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

Postdoctoral Fellow – Stem Cell Biology (City of Hope)

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