ESC & iPSC News Volume 12.16 | Apr 26 2017

TOP STORY

Human Pluripotent Stem Cells Recurrently Acquire and Expand Dominant Negative P53 Mutations

Investigators sequenced the protein-coding genes of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use. They applied computational strategies for identifying mutations present in a subset of cells in each hES cell line. Although such mosaic mutations were generally rare, they identified five unrelated hES cell lines that carried six mutations in the TP53 gene that encodes the tumor suppressor P53. [Nature] Abstract | Press Release

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A Three-Dimensional Model of Human Lung Development and Disease from Pluripotent Stem Cells

The authors report the generation from human pluripotent stem cells of lung bud organoids that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel three dimensional culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation. [Nat Cell Biol] Abstract

Metabolic Control of Primed Human Pluripotent Stem Cell Fate and Function by the miR-200c–SIRT2 Axis

Scientists report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed human pluripotent stem cells and that SIRT2 critically regulated metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Their results identified the miR-200c–SIRT2 axis as a key regulator of metabolic reprogramming, via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function. [Nat Cell Biol] Abstract

Active and Poised Promoter States Drive Folding of the Extended HoxB Locus in Mouse Embryonic Stem Cells

Researchers investigated the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem cells. While CTCF occupancy alone failed to predict the in vivo folding, they found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fiber fully explain the HoxB folding patterns imaged in single cells. [Nat Struct Mol Biol] Abstract

Direct Comparison of Distinct Naive Pluripotent States in Human Embryonic Stem Cells

Until recently, human embryonic stem cells (hESCs) were shown to exist in a state of primed pluripotency, while mouse embryonic stem cells display a naive or primed pluripotent state. Investigators showed the rapid conversion of in-house-derived primed hESCs on mouse embryonic feeder layer to a naive state in naive conversion media, in naive human stem cell media, and using the reverse-toggle protocol. [Nat Commun] Full Article

Exploiting Induced Pluripotent Stem Cell-Derived Macrophages to Unravel Host Factors Influencing Chlamydia trachomatis Pathogenesis

The authors describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage–Chlamydia interactions in vitro. They showed that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimics the infection of human blood-derived macrophages. [Nat Commun] Full Article | Press Release

The Ubiquitin Ligase LIN41/TRIM71 Targets p53 to Antagonize Cell Death and Differentiation Pathways during Stem Cell Differentiation

To better understand the specific contributions of the E3 ligase activity for the stem cell functions of LIN41, researchers characterized global changes in ubiquitin or ubiquitin-like modifications using Lin41-inducible mouse embryonic stem cells. The tumor suppressor protein p53 was among the five most strongly affected proteins in cells undergoing neural differentiation in response to LIN41 induction. [Cell Death Differ] Full Article

KAT-Independent Gene Regulation by Tip60 Promotes ESC Self-Renewal but Not Pluripotency

The authors showed that the Tip60 lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs certain functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance. [Cell Rep] Full Article | Graphical Abstract

Calreticulin Is Required for TGF-β-Induced Epithelial-to-Mesenchymal Transition during Cardiogenesis in Mouse Embryonic Stem Cells

Using embryoid bodies (EBs) derived from calreticulin-null and wild-type (WT) embryonic stem cells, scientists showed that expression of epithelial-to-mesenchymal transition and cardiac differentiation markers is induced during differentiation of WT EBs. This induction was inhibited in the absence of calreticulin and could be mimicked by inhibiting TGF-β signaling in WT cells. [Stem Cell Reports] Full Article | Graphical Abstract

iPSC-Derived Regulatory Dendritic Cells Inhibit Allograft Rejection by Generating Alloantigen-Specific Regulatory T Cells

Researchers generated regulatory dendritic cell (DCregs) from murine induced pluripotent stem cells (iPSCs), which could remain in a “stable immature stage” even under strong stimulation. Harnessing this characteristic, they hypothesized that iPS-DCregs worked as a negative vaccine to generate regulatory T cells, and induced donor-specific allograft acceptance. [Stem Cell Reports] Full Article | Graphical Abstract

Detailed Comparison of Retroviral Vectors and Promoter Configurations for Stable and High Transgene Expression in Human Induced Pluripotent Stem Cells

In order to identify the most suitable retroviral expression system in induced pluripotent stem cells, investigators systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements, and several envelope pseudotypes. Lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein were superior to gammaretroviral and alpharetroviral vectors and other envelopes tested. [Gene Ther] Abstract

Induced Pluripotent Stem Cell Modeling of Gaucher’s Disease: What Have We Learned?

The authors review induced pluripotent stem cell models of Gaucher’s disease and summarize what scientists have learned from this system. [Int J Mol Sci] Full Article

Deubiquitylating Nanog: Novel Role of USP21 in Embryonic Stem Cell Maintenance

Three groups independently identified ubiquitin-specific peptidase 21 (USP21) as an efficient deubiquitylase that reverses Nanog polyubiquitylation and stabilizes Nanog protein. A scientist has summarized the work of these three groups. [Signal Transduct Target Ther] Full Article

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Cellular Dynamics International Signs Collaboration Agreement with Harvard University Stem Cell Institute

Cellular Dynamics International announced it has signed a collaboration agreement with the Harvard University Stem Cell Institute (HSCI), a novel network of stem cell scientists that extends from the university to its affiliated hospitals and partners with the biomedical industry. The objective of the new partnership is to increase the availability of induced pluripotent stem cells and services to the HSCI network and the Boston area research community at large. [Cellular Dynamics International] Press Release

Tianzhou-1 Experiments to Put Stem Cells to the Space Test

A team lead by Tsinghua University professor Kehkooi Kee will research how weak gravity affects the development of human embryonic stem cells in space. In another stem cell experiment, scientists from the Institute of Zoology of the Chinese Academy of Sciences will study the effects of microgravity on how stem cells multiply and form into cells with different functions. The spacecraft is carrying embryonic stem cells and embryoid bodies of mice, which scientists plan to observe in space through telescope images, and compare the results with experiments conducted on the ground. [South China Morning Post] Press Release

Addressing the Ethical Issues Raised by Synthetic Human Entities with Embryo-Like Features

The “14-day rule” for embryo research stipulates that experiments with intact human embryos must not allow them to develop beyond 14 days or the appearance of the primitive streak. However, recent experiments showing that suitably cultured human pluripotent stem cells can self-organize and recapitulate embryonic features have highlighted difficulties with the 14-day rule and led to calls for its reassessment. [Elife] Full Article

California’s $3-Billion Bet on Stem Cells Faces Final Test

When California voters approved US$3 billion in funding for stem-cell research in 2004, biologists flocked to the state, and citizens dreamed of cures for Parkinson’s disease and spinal-cord injuries. Now, the pot of money — one of the biggest state investments in science — is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research. [Nature News] Editorial

NSF’s Uphill Road to Making Prestigious Early Career Award More Diverse

Only five women have won the National Science Foundation’s (NSF) annual Alan T. Waterman Award in its 41-year history, and no woman of color has ever been selected. The 2017 winners announced this month mark the 13^th year in a row that the $1 million research prize has gone to a man (two, actually, including the second black scientist ever chosen.) [ScienceInsider] Editorial

Cancer Institute Reinstates Director after Uproar from Staff and Funder

Eight days after learning via email that she was no longer the head of the Huntsman Cancer Institute in Salt Lake City, cell biologist Mary Beckerle has been invited to reassume her position. The announcement from University of Utah President David Pershing seeks to smooth a tense relationship between the semiautonomous center, its main philanthropic funder and the university that houses it. [ScienceInsider] Editorial

The Broad Institute Is Testing the Limits of What ‘Nonprofit’ Means

When a federal patent court ruled that the nonprofit Broad Institute of MIT and Harvard could legally license its version of the CRISPR-Cas9 genome-editing system, it opened the door to millions of dollars of revenue for the institute. It also contributed to the seismic shift occurring in science whereby tax-exempt research institutes established under an emerging model of “free market philanthropy” can amass money to further their research and protect their commercial interests. [STAT News] Editorial

NEW 5^th Annual German Stem Cell Network (GSCN) Conference
September 11-13, 2017
Jena, Germany

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

NEW Postdoctoral Position – Cellular Modeling of Diabetes (University of California, San Diego)

Research Associate – Research and Development (STEMCELL Technologies, Inc.)

Research Scientist – Stem Cell Biology (National Eye Institute, National Institutes of Health)

Postdoctoral Research Associate – Stem Cell Technology (Keck School of Medicine, University of Southern California)

Postdoctoral Position – Epigenetics of Pluripotent Stem Cells (Albert Einstein College of Medicine)

Research Scientist – Stem Cell Biology (ArunA Biomedical, Inc.)

Postdoctoral Fellow – Epigenetic Mechanisms (European Molecular Biology Laboratory)

Postdoctoral Fellow – Stem Cells and Epigenetics (University of Michigan)

Postdoctoral Fellow – Transcriptional Networks (Radboud University)

Independent Group Leaders – Regenerative Medicine (Center for Regenerative Medicine)

Group Leader – Induced Pluripotent Stem Cells and Brain Malignancies (German Cancer Research Center)

Postdoctoral Research Associate – Developmental Neuroscience (University of Nebraska Medical Center)

Postdoctoral Fellow – Bone Regeneration and Stem Cell Biology (New York University Medical Center)

Postdoctoral Fellow – Multiple Areas (University of Oklahoma)

Assistant or Associate Member – Stem CellGene Therapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Pluripotent Stem Cell Technology (University of California, Davis)

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