ESC & iPSC News Volume 8.06 | Feb 13 2013

NANOG-Dependent Function of Ten-Eleven Translocation 1 (TET1) and TET2 in Establishment of Pluripotency
Whereas the genomic occupancy of NANOG has been extensively investigated, comparatively little is known about NANOG-associated proteins and their contribution to the NANOG-mediated reprogramming process. Using enhanced purification techniques and a stringent computational algorithm, researchers identified 27 high-confidence protein interaction partners of NANOG in mouse embryonic stem cells. [Nature]
Abstract | Press Release

Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation
Polycomb repressive complex 1 (PRC1) catalyzes lysine 119 monoubiquitylation on H2A (H2AK119ub1) and regulates pluripotency in embryonic stem cells (ESCs). Researchers showed that Fbxl10 interacts with Ring1B and Nspc1, forming a noncanonical PRC1 that is required for H2AK119ub1 in mouse ESCs. [Mol Cell] Abstract | Graphical Abstract | Press Release

Transgene-Free iPSCs Generated from Small Volume Peripheral Blood Non-Mobilized CD34+ Cells
Investigators report a method for deriving induced pluripotent stem cells (iPSCs) from peripheral blood hematopoietic stem cells (HSCs) using immunobead purification and 2-4 day culture to enrich CD34⁺ HSCs to 80±9%, followed by reprogramming with loxP-flanked polycistronic (human Oct4, Klf4, Sox2, and c-Myc) STEMCCA-loxP lentivector; or with Sendai vectors. [Blood] Abstract

Astrocyte Pathology and the Absence of Non-Cell Autonomy in an Induced Pluripotent Stem Cell Model of TDP-43 Proteinopathy
Researchers describe a unique platform to address the question of cell autonomy in transactive response DNA-binding protein (TDP-43) proteinopathies. They generated functional astroglia from human induced pluripotent stem cells carrying an amyotrophic lateral sclerosis-causing TDP-43 mutation and showed that mutant astrocytes exhibit increased levels of TDP-43, subcellular mislocalization of TDP-43, and decreased cell survival. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Prospective Isolation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitors that Integrate into Human Fetal Heart Tissue
Researchers have prospectively identified a population of human ES cell (hESC)-derived ROR2⁺/CD13⁺/KDR⁺/PDGFRα⁺ cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. They then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2⁺/CD13⁺/KDR⁺/PDGFRα⁺ cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, the researchers show structural and functional integration of hESC-derived cardiovascular progenitors into human heart. [Proc Natl Acad Sci USA] Abstract

Nanotopographical Cues Augment Mesenchymal Differentiation of Human Embryonic Stem Cells
Using planar polycarbonate substrates lacking in topographical cues and substrates displaying a nanotopographical pattern, mesenchymal differentiation of human embryonic stem cells is directed in the absence of chemical factors and without induction of differentiation by embryoid body formation. Cells incubated on nanotopographical substrates show enhanced expression of mesenchymal or stromal markers and expression of early osteogenic progenitors at levels above those detected in cells on planar substrates in the same basal media. [Small] Abstract | Press Release

Matrix Remodeling Maintains ESC Self-Renewal by Activating Stat3
The embryonic stem cell (ESC) matrix is continuously remodeled by matrix metalloproteinases (MMPs), a process that the authors find is enhanced by the presence of mouse embryonic fibroblast feeders in a paracrine manner. Matrix remodeling by MMPs aids in the self-renewal of ESCs, as inhibition of MMPs inhibits the ability of ESCs to self-renew. [Stem Cells] Abstract | Full Article

Induced Pluripotent Stem Cells with a Pathological Mitochondrial DNA Deletion
Researchers derived and characterized induced pluripotent stem (iPS) cells from a patient with Pearson marrow pancreas syndrome (PS). Taking advantage of the tendency for heteroplasmy to change with cell passage, the authors isolated isogenic PS-iPS cells without detectable levels of deleted mitochondrial DNA (mtDNA). They found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. [Stem Cells] Abstract

Mechanism-Based Facilitated Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes
Investigators showed that cardiomyocytes derived from multiple pluripotent human stem cell lines and types using different in vitro differentiation protocols commonly displayed immature, pro-arrhythmic action potential properties such as high-degree of automaticity, depolarized resting membrane potential, Phase 4- depolarization and delayed after-depolarization. [Circ Arrhythm Electrophysiol] Abstract

Tcf15 Primes Pluripotent Cells for Differentiation
Using yeast-two-hybrid screens, researchers have identified inhibitor of DNA binding/differentiation (Id)-regulated transcription factors that are expressed in embryonic stem cells (ESCs). One of these, Tcf15, is also expressed in the embryonic day 4.5 embryo and is specifically associated with a novel subpopulation of primed ESCs. An Id-resistant form of Tcf15 rapidly downregulates Nanog and accelerates somatic lineage commitment. [Cell Rep] Abstract | Full Article | Graphical Abstract | Press Release

ACT’s Clinical Partner Receives FDA Approval to Initiate Clinical Trial Using the Company’s hESC-Derived Cells to Treat Severe Myopia
Advanced Cell Technology, Inc.’s (ACT) clinical partner, the University of California, Los Angeles, has received approval of its Investigator Investigational New Drug Application with the US Food and Drug Administration (FDA) to initiate a Phase I/II study using ACT’s retinal pigment epithelial cells derived from human embryonic stem cells (hESCs) to treat myopic macular degeneration, commonly known as nearsightedness. [Advanced Cell Technology, Inc.] Press Release

Stem Cell Research Focusing on Autism’s Genetic Mysteries Earns $2.125 Million Grant at Robert Wood Johnson Medical School
A new five-year $2.125 million grant from the New Jersey Governor’s Council for Medical Research and Treatment of Autism will fund research of induced pluripotent stem cells that may be used to piece together the genetic pathways of autism and lead to new treatments for individuals affected by Autism Spectrum Disorder. [Robert Wood Johnson Medical School] Press Release

Europe’s Leaders Slash Proposed Research Budget
In an acrimonious meeting of the European Council to decide the European Union’s general budget for 2014-2020, leaders of the Union’s 27 member states slashed the €77.6 billion research budget proposed by the European Commission back to €69.24 billion. [European Council, European Union] Press Release

Lofty Goals in Spanish Research Plan. But Very Little Money
The Spanish government has issued a new road map for science that sets high goals for the national research system, but researchers are disappointed that it has little new money to offer. Instead, the government hopes corporate funding will increase dramatically, which the scientific community says is not likely to happen. [Spanish Strategy of Science, Technology, and Innovation, Spain] Press Release

NEW Clinical Translation of Stem Cells 2013
April 22-23, 2013
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September 5-6, 2013
London, United Kingdom

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Senior QC Analyst/Assay Development Associate (StemCells, Inc.)

Postdoctoral Position – Cardiovascular Regenerative Therapies (University of California, Los Angeles)

Senior Postdoctoral Position (Vrije Universiteit Brussel, Department of Biology)

Postdoctoral Scientist (Medical Research Council [National Institute for Medical Research])

Postdoctoral Research Fellow – iPS Cell Biology (National University of Singapore, Life Sciences Institute)

Postdoctoral Position – Stem Cell Biology (Stony Brook University Medical Center)

Postdoctoral Position – Stem Cell and Neurodegenerative Diseases (University of Connecticut Health Center)

Postdoctoral Position – iPS Cells in CNS Diseases (AbbVie Deutschland GmbH & Co. KG)

Research Associate (Mount Sinai Hospital School of Medicine)


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