ESC & iPSC News Volume 14.08 | Mar 6 2019

TOP STORY

Synergy with TGFβ Ligands Switches WNT Pathway Dynamics from Transient to Sustained during Human Pluripotent Cell Differentiation

Researchers showed that β-catenin signaling responded adaptively to constant WNT signaling in PSCs, and that these dynamics became sustained on differentiation. TGFβ superfamily ligands Activin and BMP, which coordinate with WNT signaling to pattern the gastrula, increased the β-catenin response in a manner independent of their ability to induce new WNT ligand production. [Proc Natl Acad Sci USA] Abstract | Press Release

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Human Pluripotent Stem Cell-Derived Tumor Model Uncovers the Embryonic Stem Cell Signature as a Key Driver in Atypical Teratoid/Rhabdoid Tumor

The authors established human SMARCB1-deficient PSCs (hPSCs). SMARCB1-deficient hPSC-derived neural progenitor-like cells (NPLCs) efficiently gave rise to brain tumors when transplanted into the mouse brain. Notably, activation of an ESC-like signature confered a rhabdoid histology in SMARCB1-deficient NPLC-derived tumors and caused a poor prognosis. [Cell Rep] Full Article | Graphical Abstract

Rapid Changes in Morphogen Concentration Control Self-Organized Patterning in Human Embryonic Stem Cells

Investigators used human ESCs (hESCs) to address how changing morphogen levels influence differentiation, focusing on how BMP4 and Nodal signaling govern the cell-fate decisions associated with gastrulation. They showed that the BMP4 response was concentration dependent, but that expression of many Nodal targets depended on rate of concentration change. [eLife] Full Article

Single-Cell RNA Sequencing of Human Embryonic Stem Cell Differentiation Delineates Adverse Effects of Nicotine on Embryonic Development

Scientists performed single-cell RNA sequencing of human ESC-derived embryoid body (EB) in the presence or absence of nicotine. Nicotine induced lineage-specific responses and dysregulated cell-to-cell communication in EBs, shedding light on the adverse effects of nicotine on human embryonic development. [Stem Cell Reports] Full Article | Press Release | Graphical Abstract

Differentiation of Human Induced Pluripotent Stem Cells into Leydig-Like Cells with Molecular Compounds

Investigators report that Leydig-like cells (LCs) could be derived from human iPSCs using a novel differentiation protocol based on molecular compounds. When iPSC-LCs labeled with lipophilic red dye were transplanted into rat testes that had selectively eliminated endogenous LCs using EDS, the transplanted iPSC-LCs could survive and function in the interstitium of testes, and accelerate the recovery of serum testosterone levels and testis weight. [Cell Death Dis] Full Article

A Wave of WNT Signaling Balanced by Secreted Inhibitors Controls Primitive Streak Formation in Micropattern Colonies of Human Embryonic Stem Cells

Researchers used a human ESC micropattern system to model the formation of the primitive streak by WNT. In the pluripotent state E-cadherin transduced boundary forces to focus WNT signaling to the colony border. [Development] Abstract

A Proteomic Time Course through the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells

Scientists interrogated the proteome during stepwise differentiation of human iPSCs into hepatocyte-like cells over 40 days. Whole cell protein lysates were collected and analysed using stabled isotope labeled mass spectrometry based proteomics. [Sci Rep] Full Article

Extensive Reprogramming of the Nascent Transcriptome during iPSC to Hepatocyte Differentiation

Using GRO-Seq, the authors provided the first genome-wide analysis of nascent RNAs in iPSCs, hepatocyte-like cells and primary hepatocytes to extend the understanding of the transcriptional changes occurring during the hepatic differentiation process. [Sci Rep] Full Article

WNT Inhibition and Increased FGF Signaling Promotes Derivation of Less Heterogeneous Primed Human Embryonic Stem Cells, Compatible with Differentiation

Investigators showed that DMEM/F12 basal medium (DhiFI) conditions improved primed human ESC (hESC) traits, such as conferring a primed transcriptional signature with high levels of pluripotency markers and reduced levels of differentiation markers. When triggered to differentiate to neuronal and cardiac lineages, DhiFI hESCs and isogenic primed hESCs progressed similarly. [Stem Cells Dev] Abstract

Selective Elimination of Undifferentiated Human Pluripotent Stem Cells Using Pluripotent State-Specific Immunogenic Antigen Glypican-3

Human iPSCs (hiPSCs) uniquely expressed glypican-3 (GPC3) in pluripotent states and were rejected by GPC3-reactive cytotoxic T lymphocytes (CTLs), which were sensitized with human leukocyte antigen-class I-restricted GPC3 peptides. Furthermore, GPC3-reactive CTLs selectively removed undifferentiated PSCs from hiPSC-derivatives in vitro and inhibited tumor formation in vivo. [Biochem Biophys Res Commun] Abstract

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iPS-Cell Technology and the Problem of Genetic Instability – Can It Ever Be Safe for Clinical Use?

The potential of iPSC in the treatment of human disease is evaluated in light of what is known about the reprogramming process, the behavior of cells in culture, and the performance of iPSC in pre-clinical studies. [J Clin Med] Full Article

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Kadimastem Announces the Completion of Cell Transplantation of AstroRx^® in ALS Patients for Cohort A

Kadimastem announced the completion of cell transplantation (AstroRx^®) in five patients who were enrolled in cohort A for its clinical trial in ALS. AstroRx^® contains functional healthy astrocytes derived from human ESCs that aim to protect ALS-diseased motor neurons through several mechanisms. [Kadimastem] Press Release

Kinetic River Corp. Is Selected by UC Davis to Collaborate on NSF Research Grant

Kinetic River Corp. announced that it has been selected by the University of California (UC), Davis, as a subcontractor on a National Science Foundation (NSF) research grant. Prof. James Chan, the Principal Investigator on the NSF grant, is leading the effort at UC Davis to develop a label-free approach to identify stem-cell-derived cardiomyocytes. [Kinetic River Corp. (PR Newswire Association LLC.)] Press Release

The University of Oxford and Harrington Discovery Institute at University Hospitals Announce New Affiliation to Advance Therapies for Rare Diseases

The University of Oxford and University Hospitals in Cleveland, Ohio, announced a multi-year affiliation to establish a global center for rare diseases. The Oxford-Harrington Rare Disease Centre will bring together the capabilities, resources and expertise of both institutions to deliver new treatments for rare diseases, for which therapeutic options are lacking. [University Hospitals] Press Release

Head of US Food and Drug Agency Resigns

Scott Gottlieb, the head of the US Food and Drug Administration (FDA), resigned on 5 March and will depart the agency in one month. [Nature News] Editorial | Opinion

China Creating National Medical Ethics Committee to Oversee High-Risk Clinical Trials

A powerful new national medical ethics committee, which will approve all clinical trials involving high-risk biomedical technologies, is at the center of a regulatory shakeup Chinese authorities are planning in the aftermath of the widely condemned “CRISPR babies” experiment, STAT has learned. [STAT News] Editorial

NEW 2019 ASCO Annual Meeting
May 31-June 4, 2019
Chicago, Illinois, United States

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NEW Postdoctoral Fellowship – Human iPSC Research (Emory University)

NEW Research Associate – iPSC & Neurodegenerative Disease (TU Dresden)

Scientist – Stem Cell Metabolism (STEMCELL Technologies Inc.)

Scientist – Cell Culture Media and Cell Line Development (STEMCELL Technologies Inc.)

Postdoctoral Fellowship – Stem Cells & Drug Screening (Murdoch Children’s Research Institute)

Research Scientist – iPSC-Based Products (Life & Brain GMBH)

Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

Postdoctoral Research Fellow – Discovery Oncology (Merck)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

Postdoctoral Fellow – Stem Cell Biology (City of Hope)

Postdoctoral Fellow – Genetics and Epigenomics of iPSC Biology (Stanford University)

Assistant Associate Professor/Professor in Residence – Stem Cell Program (UC Davis)

Assistant/Associate Adjunct Professor – Cardiovascular Medicine (UC Davis)

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