ESC & iPSC News Volume 14.45 | Nov 20 2019

TOP STORY

Chromatin Establishes an Immature Version of Neuronal Protocadherin Selection during the Naive-to-Primed Conversion of Pluripotent Stem Cells

Researchers report a chromatin-based mechanism that emerged during the transition from the naive to the primed states of cell pluripotency and reduces, by orders of magnitude, the combinatorial potential in the human clustered protocadherin (cPCDH) locus. This mechanism selectively increased the frequency of stochastic selection of a small subset of cPCDH genes after neuronal differentiation in monolayers, ten-month-old cortical organoids and engrafted cells in the spinal cords of rats. [Nat Genet] Abstract

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Derivation of Self-Renewing Lung Alveolar Epithelial Type II Cells from Human Pluripotent Stem Cells

Investigators provide a detailed protocol for the directed differentiation of human pluripotent stem cells into self-renewing alveolar epithelial type II cell-like cells that could be maintained for up to one year in culture as epithelial-only spheres without the need for supporting mesenchymal feeder cells. [Nat Protoc] Abstract

Persistent Epigenetic Memory Impedes Rescue of the Telomeric Phenotype in Human ICF iPSCs Following DNMT3B Correction

To study whether normal DNA methylation patterns may be restored in ICF syndrome type 1 (ICF1) cells, the authors corrected DNMT3B mutations in induced pluripotent stem cells from ICF1 patients. Focusing on repetitive regions, they showed that in contrast to pericentromeric repeats, which reacquired normal methylation, the majority of subtelomeres acquired only partial DNA methylation and, accordingly, the ICF1 telomeric phenotype persisted. [eLife] Abstract

Loss of Mob1a/B Impairs the Differentiation of Mouse Embryonic Stem Cells into the Three Germ Layer Lineages

To investigate the role of Mob1a/b in stem cell maintenance and differentiation, an ESC clone in which Mob1a/b could be conditionally depleted was generated and characterized. Although Mob1a/b depletion did not affect the stemness or proliferation of mouse ESCs, this depletion caused defects in differentiation into the three germ layers. [Exp Mol Med] Full Article

Naïve Human Pluripotent Stem Cells Respond to Wnt, Nodal, and LIF Signalling to Produce Expandable Naïve Extra-Embryonic Endoderm

The authors showed that activation of Nodal and Wnt signaling drove the differentiation of naïve pluripotent cells toward extra-embryonic primitive endoderm, or hypoblast, and these could be expanded as an in vitro model for naïve extra-embryonic endoderm. [Development] Abstract

Human Induced Pluripotent Stem Cells from Two Azoospermic Patients with Klinefelter Syndrome Show Similar X Chromosome Inactivation Behavior to Female Pluripotent Stem Cells

The authors derived human (h)iPSCs by reprograming fibroblasts with episomal plasmids and applying laminin 521 as culture substrate. hiPSCs were characterized by karyotyping, immunocytochemistry, immunohistochemistry, quantitative PCR, teratoma formation, and embryoid body differentiation. X chromosome inactivation and Klinefelter syndrome (KS) hiPSC relevance were assessed by whole genome transcriptomics analysis and immunocytochemistry plus FISH of KS, healthy male and female fibroblast, and their hiPSC derivatives. [Hum Reprod] Full Article

Co-Stimulation with IL-1β and TNF-α Induces an Inflammatory Reactive Astrocyte Phenotype with Neurosupportive Characteristics in a Human Pluripotent Stem Cell Model System

Scientists induced a reactive phenotype in human (h)iPSC-derived astrocytes and studied the inflammatory natures and effects of these cells on human neurons. Astrocytes responded to interleukin-1β and tumor necrosis factor-α treatment with a typical transition to polygonal morphology and a shift to an inflammatory phenotype characterized by altered gene and protein expression profiles. [Sci Rep] Full Article

Functional Characterization of Human Pluripotent Stem Cell-Derived Cortical Networks Differentiated on Laminin-521 Substrate: Comparison to Rat Cortical Cultures

Investigators report the differentiation of functionally active human (h)PSC-derived cortical networks on defined laminin-521 substrate. They applied microelectrode array measurements to assess network events and compared the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. [Sci Rep] Full Article

Generation of Two iPSC Lines, (ICGi015-A and ICGi015-B), by Reprogramming Peripheral Blood Mononuclear Cells from a Patient with Parkinson’s Disease

With the help of non-integrating episomal vectors the iPSC lines ICGi015-A and ICGi015-B were generated from blood mononuclear cells of Parkinson’s Disease (PD) patient, carrying three SNPs, associated with PD development. The obtained iPSC lines expressed pluripotency markers and demonstrated the ability to in vitro differentiate into the three germ layers. [Stem Cell Res] Full Article

Human iPSCs-Derived Endothelial Cells with Mutation in HNF1A as a Model of Maturity-Onset Diabetes of the Young

Researchers used human (h)iPSCs from two healthy individuals to generate isogenic lines with mutation in HNF1A gene. Subsequently, control hiPSCs and their respective HNF1A clones were differentiated toward endothelial cells and different markers/functions were compared. [Cells] Abstract | Download Full Article

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Effects of Reprogramming on Genomic Imprinting and the Application of Pluripotent Stem Cells

Investigators survey the recent studies on genomic imprinting in PSCs, particularly in iPS cells. In a previous study published about six years ago, genomic imprinting was found to be variably lost in mouse iPS clones. Intriguingly, de novo DNA methylation also occurred at the previously unmethylated imprinting control regions in a high percentage of iPS clones. [Stem Cell Res] Full Article

iPSCs-Based Neural 3D Systems: A Multidimensional Approach for Disease Modeling and Drug Discovery

Models of neuropsychiatric disorders, infectious diseases, brain cancer and cerebral hypoxic injury can now be investigated from new perspectives. The authors consider the advancements made in modeling neuropsychiatric and neurological diseases with iPSC-derived organoids and their potential use to develop new drugs. [Cells] Full Article

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Lineage Cell Therapeutics Provides Update on SCiStar Clinical Study and OPC1 Spinal Cord Injury Program

Lineage Cell Therapeutics, Inc. provided an update on OPC1, the company’s oligodendrocyte progenitor cell (OPC) therapy currently being tested in a Phase I/IIa clinical trial, the SCiStar Study, for the treatment of acute spinal cord injury. [Lineage Cell Therapeutics, Inc.] Press Release

Hope Biosciences Receives FDA Approval to Commence Groundbreaking Clinical Trial for Alzheimer’s

Hope Biosciences announced that FDA has approved a Phase I/II clinical trial evaluating safety and efficacy of Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells for Alzheimer’s Disease, in partnership with Altoida, Inc., a predictive digital biomarker company. [Hope Biosciences] Press Release

European Data Law Is Impeding Studies on Diabetes and Alzheimer’s, Researchers Warn

Finland’s National Institute for Health and Welfare has sent 32,000 DNA samples to the laboratory of Francis Collins’s, director the US National Institutes of Health. But in May 2018, when European privacy law called the General Data Protection Regulationcame into force, the Finnish institute stopped all data sharing on the project, because NIH could not provide guarantees that would satisfy the institute’s interpretations of the law’s requirements. [ScienceInsider] Editorial

Science Funders Gamble on Grant Lotteries

Albert Einstein famously insisted that God does not play dice. But the Health Research Council of New Zealand does. The agency is one of a growing number of funders that award grants partly through random selection. Earlier this year, for example, David Ackerley, a biologist at Victoria University of Wellington, received NZ$150,000 (US$96,000) to develop new ways to eliminate cells – after his number came up in the council’s annual lottery. [Nature News] Editorial

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January 9-12, 2020
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NEW Research Techician – iPSC Culture Lab (University of Luxembourg)

Postdoctoral Associate – Stem Cell Research (University of Minnesota Twin Cities)

Faculty Position – Stem Cell Research (Yale University School of Medicine)

Multiple Positions – Stem Cell Biology (NIH NCATS Stem Cell Translation Laboratory)

Research Assistant – Stem Cells and Engineering (New York Blood Center)

Postdoctoral Researcher – CRISPR/Cas9 in ESCs (Institute of Molecular Biology GmbH)

Postdoctoral Researcher – iPSC Models in Neurology (IRIBHM)

Postdoctoral Scientist – Regenerative Medicine (Cedars-Sinai Medical Center)

PhD Position – Human Inducible Stem Cells (University of Fribourg)

Research Associate – Computational Image Analysis and AI (University of Bristol)

Assistant Specialist – Division of Cardiovascular Medicine (University of California, Davis)

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

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