ESC & iPSC News Volume 12.19 | May 17 2017

TOP STORY

HLA-E-Expressing Pluripotent Stem Cells Escape Allogeneic Responses and Lysis by NK Cells

Polymorphisms in the human leukocyte antigen (HLA) class I genes can cause the rejection of pluripotent stem cell-derived products in allogeneic recipients. Disruption of the Beta-2 Microglobulin gene eliminates surface expression of all class I molecules, but leaves the cells vulnerable to lysis by natural killer (NK) cells. Scientists showed that this ‘missing-self’ response can be prevented by forced expression of minimally polymorphic HLA-E molecules. [Nat Biotechnol] Abstract

(Ranked by impact factor of the journal)

Hematopoietic Stem and Progenitor Cells from Human Pluripotent Stem Cells

To yield functional human hematopoietic stem cells, the authors performed morphogen-directed differentiation of human pluripotent stem cells into hemogenic endothelium followed by screening of 26 candidate hematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage hematopoietic engraftment in mouse hosts. They recovered seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert hemogenic endothelium into hematopoietic stem and progenitor cells that engraft myeloid, B and T cells in primary and secondary mouse recipients. [Nature] Abstract | Press Release | Editorial

Modeling Psychomotor Retardation Using iPSCs from MCT8-Deficient Patients Indicates a Prominent Role for the Blood-Brain Barrier

Using patient-specific induced pluripotent stem cells (iPSCs), scientists generated monocarboxylate transporter 8 (MCT8)-deficient neural cells that showed normal thyroid hormone (TH)-dependent neuronal properties and maturation. However, the blood-brain barrier (BBB) controls TH entry into the brain, and reduced TH availability to neural cells could instead underlie the diseased phenotype. To test potential BBB involvement, they generated an iPSC-based BBB model of MCT8 deficiency, and they found that MCT8 was necessary for polarized influx of the active form of TH across the BBB. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells

Investigators showed that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner. [Cell Rep] Full Article | Press Release | Graphical Abstract

Lack of MTTP Activity in Pluripotent Stem Cell-Derived Hepatocytes and Cardiomyocytes Abolishes ApoB Secretion and Increases Cell Stress

Using induced pluripotent stem cells (iPSCs) generated from an abetalipoproteinemia (ABL) patient homozygous for a missense mutation (microsomal triglyceride transfer protein (MTTP^R46G)), the authors showed that human hepatocytes and cardiomyocytes exhibit defects associated with ABL disease, including loss of apolipoprotein B (apoB) secretion and intracellular accumulation of lipids. MTTP^R46G iPSC-derived cardiomyocytes failed to secrete apoB, accumulated intracellular lipids, and displayed increased cell death, suggesting intrinsic defects in lipid metabolism due to loss of MTTP function. [Cell Rep] Full Article | Graphical Abstract

Differentiation-Defective Human Induced Pluripotent Stem Cells Reveal Strengths and Limitations of the Teratoma Assay and In Vitro Pluripotency Assays

Scientists compared normal human pluripotent stem cells (hPSCs), induced hPSCs (hiPSCs) with reactivated reprogramming transgenes, and human embryonal carcinoma cells (hECs) in these assays. While normal hPSCs gave rise to typical teratomas, the xenografts of the hECs and the hiPSCs with reactivated reprogramming transgenes were largely undifferentiated and malignant. [Stem Cell Reports] Full Article

Accreditation of Biosafe Clinical-Grade Human Embryonic Stem Cells According to Chinese Regulations

To attain a completely xeno-free clinical-grade cell line, the system must be free of xenogenic components, the cells must have a comprehensive set of functions, and good manufacturing practice conditions must be used. In this study, following these criteria, researchers successfully derived two human embryonic stem cells (hESC) lines, which were thereby considered “clinical-grade embryonic stem cells”. In addition to the primary capacity for pluripotency, these two cell lines were efficiently differentiated into various types of clinical-grade progeny. [Stem Cell Reports] Full Article | Graphical Abstract

Three-Dimensional System Enabling the Maintenance and Directed Differentiation of Pluripotent Stem Cells under Defined Conditions

The authors showed that a three-dimensional (3D) culture system with atelocollagen porous scaffolds can significantly improve the outcome of the current platforms intended for the maintenance and lineage specification of mouse PSCs. Unlike 2D conditions, the 3D conditions maintained the undifferentiated state of mouse embryonic stem cells (mESCs) without exogenous stimulation and also supported endoderm, mesoderm, and ectoderm differentiation of mESCs under serum-free conditions. [Sci Adv] Full Article

Alzheimer’s Disease, Dementia, and Stem Cell Therapy

The authors focus on recent advances in stem cell therapies utilizing animal models of Alzheimer’s disease (AD), as well as detailing the human clinical trials of stem cell therapies for AD that are currently undergoing development. [Stem Cell Res Ther] Full Article

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CSHL to Lead International Team Developing Next-Generation Organoid Cancer Research Models

Cold Spring Harbor Laboratory (CSHL) has been awarded a research subcontract by Leidos Biomedical Research to lead a Cancer Model Development Center for pancreatic, breast, colorectal, lung, liver and other upper-gastrointestinal cancers. [Cold Spring Harbor Laboratory] Press Release

Patient Treatment Commences in Cynata’s World First Clinical Trial

Cynata Therapeutics Limited announced that the first patient has been treated with CYP-001, the company’s first mesenchymal stem cell product, in its Phase I clinical trial in patients with steroid-resistant acute graft versus host disease. [Cynata Therapeutics Limited] Press Release

China’s Belt and Road Infrastructure Plan Also Includes Science

China’s plan to make massive investments in land and sea links with global trading partners also includes a little noticed commitment to support science and engineering, including the creation of dozens of new laboratories. [ScienceInsider] Editorial

Trump Officials Act to Tilt Federal Science Boards toward Industry

Critics say that changes to advisory groups at the Environmental Protection Agency and Department of Interior could restrict or paralyze them. [Nature News] Editorial

Biology Needs More Staff Scientists

Most research institutions are essentially collections of independent laboratories, each run by principal investigators who head a team of trainees. This scheme has ancient roots and a track record of success. But it is not the only way to do science. Indeed, for much of modern biomedical research, the traditional organization has become limiting. [Nature News] Editorial

NEW Keystone Symposium: Regenerative Biology and Applications: Cell Differentiation, Tissue Organization and Biomedical Engineering
October 15-19, 2017
Pok Fu Lam, Hong Kong

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NEW 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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