ESC & iPSC News Volume 14.15 | Apr 24 2019

TOP STORY

Mammalian ISWI and SWI/SNF Selectively Mediate Binding of Distinct Transcription Factors

Researchers generated viable embryonic stem cells that lacked SNF2H, the ATPase of ISWI complexes, enabling study of SNF2H cellular function, and contrasted it to BRG1, the ATPase of SWI/SNF. Loss of SNF2H decreased nucleosomal phasing and increased linker lengths, providing in vivo evidence for an ISWI function in ruling nucleosomal spacing in mammals. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Intrinsic Apoptosis Shapes the Tumor Spectrum Linked to Inactivation of the Deubiquitinase BAP1

Investigators showed that BAP1 inactivation caused apoptosis in mouse embryonic stem cells, fibroblasts, liver, and pancreatic tissue but not in melanocytes and mesothelial cells. Ubiquitin ligase RNF2, which silenced genes by monoubiquitinating H2A, promoted apoptosis in BAP1-deficient cells by suppressing expression of the prosurvival genes Bcl2 and Mcl1. [Science] Abstract

Unbiased Detection of CRISPR Off-Targets In Vivo Using DISCOVER-Seq

The authors developed discovery of in situ Cas off-targets and verification by sequencing (DISCOVER-Seq), a universally applicable approach for unbiased off-target identification that leveraged the recruitment of DNA repair factors in cells and organisms. Tracking the precise recruitment of MRE11 uncovered the molecular nature of Cas activity in cells with single-base resolution. [Science] Abstract

Long-Range Interactions between Topologically Associating Domains Shape the Four-Dimensional Genome during Differentiation

Using a dual-lineage differentiation system, scientists reported long-range topologically associating domains (TAD)–TAD interactions that formed constitutive and variable TAD cliques. A differentiation-coupled relationship between TAD cliques and lamina-associated domains suggested that TAD cliques stabilized heterochromatin at the nuclear periphery. [Nat Genet] Abstract

Hominoid-Specific Transposable Elements and KZFPs Facilitate Human Embryonic Genome Activation and Control Transcription in Naive Human ESCs

Investigators showed that Krüppel-associated box-containing zinc finger proteins controlled the timely and pleiotropic activation of transposable element (TE)-derived transcriptional cis regulators during early embryogenesis. Evolutionarily recent SVA, HERVK, and HERVH TE subgroups contributed significantly to chromatin opening during human embryonic genome activation and are KLF-stimulated enhancers in naive human ESCs. [Cell Stem Cell] Full Article | Graphical Abstract

Reprogramming Identifies Functionally Distinct Stages of Clonal Evolution in Myelodysplastic Syndromes

Researchers demonstrated that episomal reprogramming of myelodysplastic syndromes patient samples generated iPSCs from single premalignant cells with a partial complement of mutations, directly informing the temporal order of mutations in the individual patient. Reprogramming preferentially captured early subclones with fewer mutations, which were rare among single patient cells. [Blood] Abstract

TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network

Scientists conducted a CRISPR-Cas9-mediated loss-of-function genetic screen that identified two epigenetic regulators, TAF5L and TAF6L, components or co-activators of the GNAT-HAT complexes for the mouse ESC state. Detailed molecular studies demonstrated that TAF5L/TAF6L transcriptionally activated c-Myc and Oct4 and their corresponding MYC and CORE regulatory networks. [Mol Cell] Abstract | Graphical Abstract

MicroRNA-Deficient Mouse Embryonic Stem Cells Acquire a Functional Interferon Response

The authors showed that, in the absence of miRNAs, ESCs acquired an active type I Interferon (IFN) response. Proteomic analysis identified MAVS, a central component of the IFN pathway, to be actively silenced by miRNAs and responsible for suppressing IFN expression in ESCs. [Elife] Abstract

Functional Evaluation of Transposable Elements as Enhancers in Mouse Embryonic and Trophoblast Stem Cells

Scientists tested a set of long terminal repeat transposable element (TE) families for roles as enhancers in mouse embryonic and trophoblast stem cells. Epigenomic and transcriptomic data suggested that a large number of TEs helped to establish tissue-specific gene expression programmes. Genetic editing of individual TEs confirmed a subset of these regulatory relationships. [Elife] Abstract

Efficient Neural Differentiation of Human Pluripotent Stem Cells by Extrinsic Signals Derived from Co-Cultured Neural Stem/Precursor Cells

Investigators found that undifferentiated human PSCs (hPSCs) present in the cultures of neural stem/precursor cells completely disappeared within several days when cultured under neural differentiation culture conditions. Intriguingly, the disappearance of undifferentiated cells was not due to cell death, but was instead mediated by neural conversion of hPSCs. [Mol Ther] Abstract | Graphical Abstract

Angiomotin Regulates YAP Localization during Neural Differentiation of Human Pluripotent Stem Cells

Researchers employed CRISPR/Cas9 to tag endogenous Yes-associated protein (YAP) in hPSCs and used this fusion protein to identify YAP’s interaction partners. This engineered cell line revealed that neural differentiation promoted a change in YAP interactors, including a dramatic increase in angiomotin interaction with YAP. [Stem Cell Reports] Full Article | Graphical Abstract

Influenza A Virus-Triggered Autophagy Decreases the Pluripotency of Human-Induced Pluripotent Stem Cells

Using proteomic approaches, investigators utilized human iPSCs for modeling intrablastocyst infection with influenza virus to not only investigate the vulnerability and responses of pluripotent stem cells to this virus but also to determine the possible impacts of influenza on pluripotency and signaling pathways controlling differentiation and embryogenesis. [Cell Death Dis] Full Article

Restoration of FVIII Expression by Targeted Gene Insertion in the FVIII Locus in Hemophilia a Patient-Derived iPSCs

Scientists described a universal genome correction strategy to restore coagulation factor VIII (FVIII) expression in iPSCs derived from a patient with hemophilia A by human elongation factor 1 alpha (EF1α)-mediated normal FVIII gene expression in the FVIII locus of the patient. They used the CRISPR/Cas9-mediated homology-directed repair system to insert the B-domain deleted from the FVIII gene with the human EF1α promoter. [Exp Mol Med] Full Article

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From Embryonic Stem Cells to Induced Pluripotent Stem Cells – Ready for Clinical Therapy?

The authors review the generation and uses of ESCs compared to iPSCs, and discuss their advantages and limitations. They also evaluate the feasibility of clinical therapies and the future prospects for induced pluripotent cell-based treatments. [Clin Transplant] Abstract

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

Fate Therapeutics Announces Five Presentations

Fate Therapeutics, Inc. announced that Fate scientists and collaborators will present data highlighting the company’s iPSC product platform and its iPSC-derived cell product candidates. [Press release from Fate Therapeutics, Inc. discussing research to be presented at the American Society of Gene & Cell Therapy (ASGCT) 22^nd Annual Meeting, Washington, DC] Press Release

Adaptimmune Announces Oral Presentation of Allogeneic SPEAR T-Cell Program

Adaptimmune Therapeutics plc announced an oral presentation by Dr. Jo Brewer, VP of Platform Sciences, summarizing data from Adaptimmune’s off-the-shelf SPEAR T-cell program. Its title: ‘Differentiating T-Cells from Human iPSCs to Create Off-The-Shelf SPEAR T-Cell Therapies’. [Press release from Adaptimmune Therapeutics plc discussing research presented at the American Society of Gene & Cell Therapy (ASGCT) 22^nd Annual Meeting, Washington, DC] Press Release

ExCellThera’s Lead Technology, ECT-001, Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation

ExCellThera Inc. announced that the FDA has granted RMAT designation to its lead technology, ECT-001, in the treatment of hematologic malignancies. The RMAT designation is based on strong data from Phase I/II clinical trials using ECT-001 to expand stem and immune cells for the treatment of blood cancers. [ExCellThera Inc.] Press Release

Cell Microsystems Receives New NIH Grants for Automating CRISPR Workflows

Cell Microsystems announced it has received two NIH Small Business Innovation and Research awards totaling $1.9M to automate CRISPR workflows using its proprietary CellRaft Technology. [Cell Microsystems (Business Wire, Inc.)] Press Release

After Firings, MD Anderson Officials Try to Calm Fears of Racial Profiling

Administrators at the MD Anderson Cancer Center in Houston, Texas, tried to reassure alarmed employees that its recent dismissals of faculty members alleged to have broken federal funding rules were not connected to race or ethnicity. [ScienceInsider] Editorial

FDA Hires Pew Director to Lead Regulatory Policy

Elizabeth Jungman, a well-known public health expert and a Capitol Hill veteran, will lead the FDA’s regulatory policy office starting this summer, STAT has learned. Jungman, who currently serves as head of public health programs at the Pew Charitable Trusts, will direct the FDA’s Office of Regulatory Policy, a post with sweeping authority over FDA’s human drugs portfolio, two sources told STAT. [STAT] Editorial

NEW FEBS: From Molecules to Living Systems
July 6-11, 2019
Krakow, Poland

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

NEW Research Assistant – Stem Cells & Regenerative Medicine (Boston Children’s Hospital)

NEW Postdoctoral Fellow – Pluripotent Stem Cells & Joint Tissue Development (Boston Children’s Hospital)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

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

Postdoctoral Lecturer – Stem Cell Biology & Regenerative Medicine (The University of Manchester)

Postdoctoral Fellowship – iPSCs and Differentiated Neurons (Howard Hughes Medical Institute)

Postdoctoral Fellowship – Cell Fate and Cancer Initiation (University of Miami Miller School of Medicine)

Associate Staff Scientist, Automation Systems (New York Stem Cell Foundation)

Postdoctoral Position – Human Pluripotent Stem Cell Biology (Washington University School of Medicine)

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

Staff Scientist – Transcriptional Control in Development and Disease (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow Positions – Human iPSCs, Epigenetics, Hematopoietic Stem Cell Biology, and Blood Cancers (Nationwide Children’s Hospital & Ohio State University)

Director of Operations – Biotech Production (Cincinnati Children’s Hospital Medical Center)

Postdoctoral Fellowship – Patient-Derived iPSC Research (Oklahoma Medical Research Foundation)

Postdoctoral Fellowship – Human iPSC Research (Emory University)

Postdoctoral Fellow – Genetics and Epigenomics of iPSC Biology (Stanford University)

Assistant Associate Professor/Professor in Residence – Stem Cell Program (UC Davis)

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