ESC & iPSC News Volume 12.20 | May 24 2017

TOP STORY

Aryl Hydrocarbon Receptor Inhibition Promotes Hemato-Lymphoid Development from Human Pluripotent Stem Cells

To model hematopoiesis, human embryonic stem cells (hESCs) were allowed to differentiate in defined conditions in the presence of the aryl hydrocarbon receptor (AHR) antagonist stemreginin-1 (SR-1) or AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin. The authors demonstrated a significant increase in CD34⁺CD31⁺ hemato-endothelial cells in SR-1 treated hESCs, as well as a two-fold expansion of CD34⁺CD45⁺ hematopoietic progenitor cells. [Blood] Abstract

(Ranked by impact factor of the journal)

Using hESCs to Probe the Interaction of the Diabetes-Associated Genes CDKAL1 and MT1E

Through transcript profiling, scientists found that expression of the metallothionein (MT) gene family, also linked by genome-wide association studies to diabetes, is significantly downregulated in CDKAL1^−/− cells that have been differentiated to insulin-expressing pancreatic beta-like cells. Forced MT1E expression rescued both hypersensitivity of CDKAL1 mutant cells to glycolipotoxicity and pancreatic beta-cell dysfunction in vitro and in vivo. [Cell Rep] Full Article | Graphical Abstract

Directed Differentiation of Human Pluripotent Stem Cells to Microglia

To improve the understanding of human microglial biology, the authors devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells. Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. [Stem Cell Reports] Full Article | Press Release

Expansion and Purification Are Critical for the Therapeutic Application of Pluripotent Stem Cell-Derived Myogenic Progenitors

Researchers recapitulated one prominent protocol, and showed that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation. They incorporated the inducible PAX7 lentiviral system into this protocol, which then enabled scalable expansion of a homogeneous population of skeletal myogenic progenitors capable of forming myofibers in vivo. [Stem Cell Reports] Full Article

Identification of a Small Molecule that Facilitates the Differentiation of Human iPSCs/ESCs and Mouse Embryonic Pancreatic Explants into Pancreatic Endocrine Cells

Investigators aimed to establish efficient differentiation protocols to change human induced pluripotent stem cells (hiPSCs)/human embryonic stem cells (hESCs) to insulin⁺ cells using novel small-molecule inducers. Sodium cromoglicate improved the generation of pancreatic endocrine cells from multiple hiPSC/hESC lines and mouse embryonic pancreatic explants by facilitating the differentiation of endocrine precursors. [Diabetologia] Abstract

Induced Pluripotent Stem Cell Modeling of HLHS Underlines the Contribution of Dysfunctional NOTCH Signaling to Impaired Cardiogenesis

Scientists generated induced pluripotent stem cells (iPSCs) from five hypoplastic left heart syndrome (HLHS) patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype. Their data indicated that HLHS-iPSCs have a reduced ability to give rise to mesodermal, cardiac progenitors and mature cardiomyocytes and an enhanced ability to differentiate to smooth muscle cells. [Hum Mol Genet] Abstract | Full Article

PRMT8 Controls the Pluripotency and Mesodermal Fate of Human Embryonic Stem Cells by Enhancing the PI3K/AKT/SOX2 Axis

Protein arginine methyltransferases 8 (PRMT8) was expressed and then its level gradually decreased during spontaneous differentiation of human embryonic stem cells (hESCs). PRMT8 loss- or gain-of-function studies demonstrated that PRMT8 contributed to longer maintenance of hESC pluripotency, even under basic fibroblast growth factor-deprived conditions. [Stem Cells] Abstract

An Episomal Vector-Based CRISPR/Cas9 System for Highly Efficient Gene Knockout in Human Pluripotent Stem Cells

The authors developed an episomal vector-based CRISPR/Cas9 system, which they called epiCRISPR, for highly efficient gene knockout in human pluripotent stem cells. The epiCRISPR system enabled generation of up to 100% insertion/deletion rates. The epiCRISPR system enabled efficient double-gene knockout and genomic deletion. [Sci Rep] Full Article

Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

The impairment of autophagic and proteasomal cleansing together with changes in pigmentation has been documented in retinal pigment epithelial (RPE) cell degeneration. Researchers showed that inhibition of proteasomal degradation with MG-132 or autophagy with bafilomycin A1 increased the accumulation of premelanosomes and autophagic structures in human embryonic stem cell-derived RPE cells. [Int J Mol Sci] Full Article

Efficient, Selective Removal of Human Pluripotent Stem Cells via Ecto-Alkaline Phosphatase-Mediated Aggregation of Synthetic Peptides

Investigators explored the potential of phospho-D-peptides as novel induced pluripotent stem cell (iPSC)-eliminating agents. Alkaline phosphatases overexpressed on iPSCs dephosphorylate phospho-D-peptides into hydrophobic peptides that aggregate and induce cell death. They isolated a peptide candidate, D-3, that selectively and rapidly induced toxicity in iPSCs within one hour but had little influence on various non-iPSCs, including primary hepatocytes and iPSC-derived cardiomyocytes. [Cell Chem Biol] Abstract | Graphical Abstract

Injection of Embryonic Stem Cell Derived Macrophages Ameliorates Fibrosis in a Murine Model of Liver Injury

Scientists describe a protocol whereby pure populations of therapeutic macrophages can be produced in vitro from murine embryonic stem cells on a large scale. Embryonic stem cell derived macrophages displayed comparable morphology and cell surface markers to bone marrow derived macrophages but their novel imaging technique revealed that their phagocytic index was significantly lower. [NPJ Regen Med] Full Article

Concise Review: Induced Pluripotent Stem Cell-Based Drug Discovery for Mitochondrial Disease

The authors discuss the promises and challenges of induced pluripotent stem cell (iPSC)-based drug discovery for mitochondrial disease with a specific focus on neurological conditions. They anticipate that a proper use of the potent iPSC technology will provide critical support for the development of innovative therapies against untreatable and detrimental disorders. [Stem Cells] Full Article

Mechanism of Human Somatic Reprogramming to iPS Cell

In the last decade, puzzle pieces of somatic reprogramming have been collected with difficulty. Collectively, dissecting reprogramming events and identification of the hallmark of sequentially activated/silenced genes have revealed mouse somatic reprogramming in fragments, but there is a long way to go toward understanding the molecular mechanisms of human somatic reprogramming, even with developing technologies. [Lab Invest] Abstract

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

NewStem Introduces Novel Technology for Predicting Resistance to Chemotherapies

NewStem introduces a novel technology for predicting resistance to chemotherapy treatments. The company is developing a diagnostic kit based on the pioneering research of Professor Nissim Benvenisty, the Azrieli Center for Stem Cells and Genetic Research, the Hebrew University of Jerusalem, in the field of human haploid pluripotent stem cells. [Yissum Ltd.] Press Release

Investing in Innovation

Massachusetts Life Sciences Center (MLSC) gives Boston biomedicine an $18 million boost. Four new projects, each run by Boston-based members of the Harvard biomedical research community, are funded by the new capital infrastructure grants from the MLSC. [Harvard Medical School] Press Release

TEDCO Announces $8.5 Million in New Stem Cell Program Awards via Maryland Stem Cell Research Commission

The Maryland Stem Cell Research Commission approved funding for 29 awards for a total of $8,533,987. These awards will be distributed between six different research institutes and six companies and will address over 20 different diseases and conditions. [Maryland Technology Development Corporation (TEDCO)] Press Release

Academies Calculate How Much Brexit Will Cost U.K. Researchers

Some academic fields in the United Kingdom (U.K.) will have major funding holes to fill once the country leaves the European Union, according to new research commissioned by four U.K. academies. The Academy of Medical Sciences, the British Academy, the Royal Academy of Engineering, and the Royal Society commissioned the Technopolis Group, an independent policy research organization, to find out in detail just how reliant U.K. science is on European funding. The €1.1 billion per year that U.K. research now gets from Europe is, the report found, spread across all academic disciplines it analyzed but some fields will have a tougher time than others finding alternative sources. [ScienceInsider] Editorial

What’s in Trump’s 2018 Budget Request for Science?

President Donald Trump unveiled his full 2018 budget request to Congress. The spending plan, for the fiscal year that begins 1 October, fleshes out the so-called skinny budget that the White House released this past March. That plan called for deep cuts to numerous research agencies. [ScienceInsider] Editorial

NEW Developmental Biology and Regeneration
October 25-27, 2017
Stockholm, Sweden

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NEW Scientific Sales Representative – Media (STEMCELL Technologies Inc.)

NEW Postdoctoral Position – Regulation of Embryonic Stem Cells (Joslin Diabetes Center)

Senior/Principle Research Associate – Cell and Molecular Biology (Editas Medicine)

Assistant Professor – Stem Cell and Regenerative Biology (Harvard University)

Postdoctoral Research Scientist – Cardiovascular (Columbia University Medical Center)

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

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)

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

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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