ESC & iPSC News Volume 13.15 | Apr 18 2018

TOP STORY

Pluripotency Factors Functionally Premark Cell-Type-Restricted Enhancers in ES Cells

Scientists showed that cell-type-restricted enhancers are ‘premarked’ and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. [Nature] Abstract

(Ranked by impact factor of the journal)

Pluripotency Transcription Factors and Tet1/2 Maintain Brd4-Independent Stem Cell Identity

Investigators showed that Brd4 is dispensable for self-renewal and pluripotency of ESCs. When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression. [Nat Cell Biol] Abstract

Defining Essential Genes for Human Pluripotent Stem Cells by CRISPR-Cas9 Screening in Haploid Cells

Researchers generated a genome-wide loss-of-function library targeting 18,166 protein-coding genes to define the essential genes in human PSCs. With this, they could allude to an intrinsic bias of essentiality across cellular compartments, uncover two opposing roles for tumor suppressor genes and link autosomal-recessive disorders with growth-retardation phenotypes to early embryogenesis. [Nat Cell Biol] Abstract

ERF Deletion Rescues RAS Deficiency in Mouse Embryonic Stem Cells

The authors showed that RAS nullyzygosity reduces the growth of mouse ESCs and prohibits their differentiation. Upon RAS deficiency or MEK inhibition, ERF (E twenty-six 2 [Ets2]-repressive factor), a transcriptional repressor from the ETS domain family, translocated to the nucleus, where it bound to the enhancers of pluripotency factors and key RAS targets. [Genes Dev] Abstract

NKX2–5 Regulates Human Cardiomyogenesis via a HEY2 Dependent Transcriptional Network

Scientists showed deletion of NKX2–5, a critical component of the cardiac gene regulatory network, in human ESCs, results in impaired cardiomyogenesis, failure to activate VCAM1 and to downregulate the progenitor marker PDGFRα. [Nat Commun] Full Article

Global H3.3 Dynamic Deposition Defines Its Bimodal Role in Cell Fate Transition

Researchers investigated the dynamic changes in the deposition of the histone variant H3.3 during cellular reprogramming. H3.3 maintained the identities of the parental cells during reprogramming as its removal at early time-point enhances the efficiency of the process. [Nat Commun] Full Article

Silencing of Transposable Elements May Not Be a Major Driver of Regulatory Evolution in Primate iPSCs

To investigate the evolution of transposable element (TE) silencing, the authors performed H3K9me3 ChIP-seq experiments in induced pluripotent stem cells from ten human and seven chimpanzee individuals. They identified four million orthologous TEs and found the SVA and ERV families to be marked most frequently by H3K9me3. [eLife] Abstract | Full Article

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal

Scientists explored the essential role of the polyamines in the promotion of self-renewal and identify a new stem cell regulator that acts downstream of the polyamines: MINDY1. Overexpression of MINDY1 promoted ESC self-renewal in the absence of the usually essential cytokine LIF. [Stem Cells] Abstract

Wnt Signal Activation Induces Midbrain Specification through Direct Binding of the Beta-Catenin/TCF4 Complex to the EN1 Promoter in Human Pluripotent Stem Cells

The authors found that activating the canonical Wnt signal significantly upregulated the expression of engrailed 1 (EN1), a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells. [Exp Mol Med] Full Article

Comparative Analysis of Naive, Primed and Ground State Pluripotency in Mouse Embryonic Stem Cells Originating from the Same Genetic Background

Researchers performed a comprehensive characterization of naive, primed and ground state mouse ESCs originating from the same genetic background within their laboratory, by comparing their transcriptional profiles. [Sci Rep] Full Article

Contrasting Epigenetic States of Heterochromatin in the Different Types of Mouse Pluripotent Stem Cells

Investigators present a comparative study of the epigenetic and transcriptional states of pericentromeric heterochromatin satellite sequences found in pluripotent states. They showed that two kinase inhibitor-ESCs are distinguished from other pluripotent cells by a prominent enrichment in H3K27me3 and low levels of DNA methylation at pericentromeric heterochromatin. [Sci Rep] Full Article

Single-Cell Transcriptional Profiling: A Window into Embryonic Cell-Type Specification

The authors discuss recent advances in single-cell transcriptomics and imaging and provide a brief outline of current bioinformatics methods available to analyze the resulting data. They then discuss how these techniques have contributed to an understanding of pre-implantation and early post-implantation development and of in vitro pluripotency. [Nat Rev Mol Cell Biol] Abstract

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

Data from BioTime’s OpRegen^® and Retinal Restoration Programs to Be Presented

BioTime, Inc. announced that data from the ongoing OpRegen^® clinical trial and Retinal Restoration program will be presented. [Press release from BioTime, Inc. discussing research to be presented at the 2018 Association for Research in Vision and Ophthalmology (ARVO), Honolulu] Press Release

$10 Million Grant Supports Research on Disease Prevention, Fasting and Aging

A new, $10 million program grant from the National Institute on Aging awarded to USC and Harvard University researchers focuses on interventions that could protect against aging and diseases, in part by causing the regeneration of cells, systems and organs. [University of Southern California] Press Release

CU Anschutz Scientists Awarded $3.8 Million DOD Grant

Scientists from the Gates Center for Regenerative Medicine at the University of Colorado (CU) School of Medicine are part of a consortium awarded $3.8 million from the U.S. Department of Defense (DOD) to move discoveries in stem cell-created skin grafts into the manufacturing stage, bringing further hope to victims of debilitating inherited skin diseases. [University of Colorado School of Medicine] Press Release

ViaCyte Awarded NIH SBIR Grant to Support In Vitro Development of Stem Cell-Derived Functional Human Pancreatic Beta Cells

ViaCyte, Inc. announced that it has been awarded a Small Business Innovative Research (SBIR) Phase II Award from the National Institute of Diabetes and Digestive and Kidney Diseases to support the further development of functional human beta cells in vitro. [ViaCyte, Inc.] Press Release

University Declines to Sanction Doctor Who Referred Patient for Deadly Transplant

The doctor who referred a cancer patient for the first-ever artificial trachea implant will not face disciplinary action from the University of Iceland in Reykjavik, where he works. Patient Andemariam Beyene died after the implant, a polymer scaffold seeded with his own stem cells, failed. [ScienceInsider] Editorial

Spain’s Biggest-Ever Science Petition Decries ‘Abandonment’ of Research

Leading Spanish scientific organizations delivered a petition signed by more than 277,000 people to the national parliament in Madrid, calling on the government to stop the “progressive abandonment of science in Spain” caused by budget cuts. The petition is the largest ever on a science-policy subject in Spain. [Nature News] Editorial

Panel Calls for a Postdoc Tax and Other Measures to Help Biomedical Scientists Find Jobs

The U.S. Congress, federal funding agencies, universities, and other research institutions must take significant steps, such as a postdoc “tax” and a hard cap on how long postdocs can be funded by a lab head, to better usher young biomedical scientists into viable careers, a committee from the National Academies of Sciences, Engineering, and Medicine concluded in a report. [ScienceInsider] Editorial

African Scientists Call for More Control of Their Continent’s Genomic Data

Africa-based researchers issued guidelines for the ethical handling of samples for genomic studies. The voluntary rules are an effort to combat ‘helicopter’ research, in which foreign scientists take samples and data from communities and then return to their home institutions. [Nature News] Editorial

NEW 6^th Annual German Stem Cell Network (GSCN) Conference
September 19-21, 2018
Heidelberg, Germany

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

NEW Postdoctoral Fellow – Cardiovascular Tissue Engineering (Stanford University)

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

Postdoctoral Positions – Organoids and Induced Pluripotent Stem Cells (Max Planck for Molecular Biomedicine)

Research Associate – Regulatory Dynamics and Cell Identity (Imperial College London)

Postdoctoral Positions – Translational iPS Cell Research, Division of Pre-Clinical Innovation (National Center for Advancing Translational Sciences)

Associate/Assistant Professor(s) – Disease Modeling with Human Induced Pluripotent Stem Cells (The Chinese University of Hong Kong)

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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