ESC & iPSC News Volume 10.14 | Apr 15 2015

ESC & iPSC News 10.14 April 15, 2015

ESC & iPSC News

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Stem Cell Disease Model Clarifies Bone Cancer Trigger
Using induced pluripotent stem cells (iPSCs), a team of researchers has gained new insight into genetic changes that may turn a well-known anti-cancer signaling gene into a driver of risk for bone cancers, where the survival rate has not improved in 40 years despite treatment advances. [Press release from Icahn School of Medicine at Mount Sinai discussing online publication in Cell] Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency
Investigators showed that the estrogen-related nuclear receptors (ERRα and ERRγ) and their partnered co-factors PGC-1α and PGC-1β are transiently induced at an early stage, resulting in a burst of oxidative phosphorylation (OXPHOS) activity. Upregulation of ERRα or ERRγ is required for the OXPHOS burst in both human and mouse cells, respectively, as well as induced pluripotent stem cell generation itself. [Cell Stem Cell] Abstract | Graphical Abstract

Pontin Functions as an Essential Coactivator for OCT4-Dependent lincRNA Expression in Mouse Embryonic Stem Cells
The authors found that pontin chromatin remodeling factor plays an essential role as a coactivator for OCT4 for maintenance of pluripotency in mouse embryonic stem (ES) cells. Genome-wide analyses revealed that pontin and OCT4 share a substantial set of target genes involved in ES cell maintenance. [Nat Commun]
Abstract | Full Article

A Cohesin–Oct4 Complex Mediates Sox Enhancers to Prime an Early Embryonic Lineage
Scientists reported a chromatin-remodeling mechanism and enhancer function that mediate cell fate switching. Oct4 alters the higher-order chromatin structure at both Sox-2 and Sox-17 loci. Oct4 titrates out cohesin and switches the Sox-17 enhancer from a locked to an active state. [Nat Commun] Abstract

Heightened Potency of Human Pluripotent Stem Cell Lines Created by Transient BMP4 Exposure
Investigators report the acquisition of a unique stem cell phenotype by both human embryonic stem cells and induced pluripotent stem cells (PSCs) in response to transient exposure to bone morphogenetic protein 4 (BMP4) plus inhibitors of ACTIVIN signaling and FGF2, followed by trypsin dissociation and recovery of colonies capable of growing on a gelatin substratum in standard medium for human PSCs at low but not high FGF2 concentrations. [Proc Natl Acad Sci USA] Abstract | Full Article

A Novel Autoregulatory Loop between the Gcn2-Atf4 Pathway and L-Proline Metabolism Controls Stem Cell Identity
Scientists demonstrated that embryonic stem cell behavior relies on a feedback loop that involves the non-essential amino acid L-Proline (L-Pro) in the modulation of the Gcn2-Eif2α-Atf4 amino acid starvation response pathway that in turn regulates L-Pro biosynthesis. [Cell Death Differ] Full Article

Molecular Signature of Erythroblast Enucleation in Human Embryonic Stem Cells
To investigate erythroblast enucleation, researchers studied the erythroid differentiation of human embryonic stem cells (hESCs). They demonstrated that terminal erythroid differentiation from hESCs is directly dependent on the age of the embryoid bodies. [Stem Cells] Abstract

piggyBac Insertional Mutagenesis Screen Identifies a Role for Nuclear RHOA in Human Embryonic Stem Cell Differentiation
Scientists present a piggyBac transposon gain of function screen in human embryonic stem cells that identified DENND2C, which genetically cooperates with NANOG to maintain self-renewal in the presence of retinoic acid. They showed that DENND2C negatively regulates RHOA activity, which cooperates with NANOG to block differentiation. [Stem Cell Reports] Full Article

Elimination of Tumorigenic Human Pluripotent Stem Cells by a Recombinant Lectin-Toxin Fusion Protein
Researchers developed a recombinant lectin-toxin fusion protein of rBC2LCN with a catalytic domain of Pseudomonas aeruginosa exotoxin A, termed rBC2LCN-PE23. rBC2LCN-PE23 bound to human pluripotent stem cells, followed by its internalization, allowing intracellular delivery of a cargo of cytotoxic protein. The addition of rBC2LCN-PE23 to the culture medium was sufficient to completely eliminate human pluripotent stem cells. [Stem Cell Reports] Full Article | Graphical Abstract

View Webinar: Genome Editing: From Modeling Disease to Novel Therapeutics

Establishing Pluripotency in Early Development
The authors review recent progress in the understanding of chromatin state and regulation of gene expression in the context of embryonic development in vertebrates, in particular mouse, Xenopus and zebrafish. They include work on mouse embryonic stem cells and highlight work that illustrates how early embryonic dynamics establish gene regulatory networks and the state of pluripotency. [Biochim Biophys Acta] Full Article

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

Mount Sinai Receives $8.8 Million Grant to Further Stem Cell Research
An $8.8 million grant from the New York State Stem Cell Science Program will accelerate efforts by the Icahn School of Medicine at Mount Sinai to develop new stem-cell-based treatments for chemotherapy-resistant blood cancer and other genetic blood disorders. [Icahn School of Medicine at Mount Sinai] Press Release

California Launches Initiative to Advance Precision Medicine
Governor Edmund G. Brown Jr. announced the creation of the California Initiative to Advance Precision Medicine to better understand disease through advanced computing and spur public-private collaboration throughout the state. UCSF will host the two-year initiative, in conjunction with UC Health, with $3 million in startup funds from the state. [State of California] Press Release

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Withholding Results from Clinical Trials is Unethical, Says WHO
The World Health Organization (WHO) issued a call to make results from every clinical study publicly available within a year. [ScienceInsider] Editorial

African Hub Set Up to Boost Research Autonomy
African scientists look set to gain greater control over research in their own countries, if an ambitious plan for a regional hub to award grants and develop research capacity bears fruit. [Nature News] Editorial

NEW ICTERM 2015 : 17th International Conference on Tissue Engineering and Regenerative Medicine
July 20-21, 2015
Paris, France

NEW Hydra XI Summer School on Stem Cell Biology
September 6-13, 2015
Hydra, Greece

NEW Cell Therapy Bioprocessing & Commercialization
September 30-October 1, 2015
Alexandria, United States

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

NEW Postdoctoral Fellowship – Stem Cells & Epigenetics (National Institutes of Health)

Scientist – Reprogramming and Pluripotent Stem Cell Biology (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Human Pluripotent Stem Cell Differentiation (Barcelona Centre for Regenerative Medicine)

PhD Position – Lineage Reprogramming (Max Delbrück Center for Molecular Medicine)

Stem Cell Culture Scientist (Paramount Recruitment)

Postdoctoral Fellowship – Stem Cells & Epigenetics (National Institutes of Health)

PhD Position – Early Human Brain Development Modeling with hiPSCs (University of Bonn)

Postdoctoral Position – Induced Pluripotent Stem Cells to Study Metabolism and Gene Expression Regulating Neural Tube Development (Joslin Diabetes Center)

Postdoctoral Research Associate – Stem Cell Engineering (Rensselaer Polytechnic Institute)

Postdoctoral Position – Human Induced Pluripotent Stem Cells (hiPSCs) and the Peripheral Nervous System (Inserm)

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