EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness.

Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis.

Optimized and Scalable Precoating-Free Reprogramming of Human Peripheral Blood Mononuclear Cells into iPSCs.

Human disease modeling has been profoundly transformed by the introduction of human induced pluripotent stem cells (iPSCs), marking the onset of a new era. This ground-breaking development offers a tailored framework for generating pluripotent cells from any individual, effectively enabling the development of cellular models for the study of human physiology and diseases on an unprecedented scale. Although technologies for iPSCs generation have advanced rapidly over the past two decades, protocols for reprogramming patient-derived somatic cells into stem cells still pose a major challenge for the development of automated pipelines capable of generating iPSCs at scales that are cost-effective, reproducible, and easy to implement.

CAG repeat expansion in the Huntington's disease gene shapes linear and circular RNAs biogenesis.

Alternative splicing (AS) appears to be altered in Huntington's disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD).

Cortical Astrocyte Progenitors and Astrocytes from Human Pluripotent Stem Cells.

Astrocytes coordinate several homeostatic processes of the central nervous system and play essential roles for normal brain development and response to disease conditions. Protocols for the conversion of human induced pluripotent stem cells (hiPSCs) into mature astrocytes have opened to the generation of systems to explore astrocytes' functions in living human cell contexts and patient-specific settings. In this study, we present an optimized monolayer procedure to commit hiPSC-derived cortical progenitors into enriched populations of cortical astrocyte progenitor cells (CX APCs) that can be further amplified and efficiently differentiated into mature astrocytes.

One-shot analysis of translated mammalian lncRNAs with AHARIBO.

A vast portion of the mammalian genome is transcribed as long non-coding RNAs (lncRNAs) acting in the cytoplasm with largely unknown functions. Surprisingly, lncRNAs have been shown to interact with ribosomes, encode peptides, or act as ribosome sponges. These functions still remain mostly undetected and understudied owing to the lack of efficient tools for genome-wide simultaneous identification of ribosome-associated and peptide-producing lncRNAs.

Artificial cells drive neural differentiation.

We report the construction of artificial cells that chemically communicate with mammalian cells under physiological conditions. The artificial cells respond to the presence of a small molecule in the environment by synthesizing and releasing a potent protein signal, brain-derived neurotrophic factor. Genetically controlled artificial cells communicate with engineered human embryonic kidney cells and murine neural stem cells.

Vertically-Aligned Functionalized Silicon Micropillars for 3D Culture of Human Pluripotent Stem Cell-Derived Cortical Progenitors.

Silicon is a promising material for tissue engineering since it allows to produce micropatterned scaffolding structures resembling biological tissues. Using specific fabrication methods, it is possible to build aligned 3D network-like structures. In the present study, we exploited vertically-aligned silicon micropillar arrays as culture systems for human iPSC-derived cortical progenitors.

Epsins Regulate Mouse Embryonic Stem Cell Exit from Pluripotency and Neural Commitment by Controlling Notch Activation.

Epsins are part of the internalization machinery pivotal to control clathrin-mediated endocytosis. Here, we report that epsin family members are expressed in mouse embryonic stem cells (mESCs) and that epsin1/2 knockdown alters both mESC exits from pluripotency and their differentiation. Furthermore, we show that epsin1/2 knockdown compromises the correct polarization and division of mESC-derived neural progenitors and their conversion into expandable radial glia-like neural stem cells.

Inducible Alpha-Synuclein Expression Affects Human Neural Stem Cells' Behavior.

Converging evidence suggest that levels of alpha-synuclein (aSyn) expression play a critical role in Parkinson's disease (PD). Several mutations of the SNCA gene, encoding for aSyn have been associated to either the familial or the sporadic forms of PD. Nonetheless, the mechanism underlying wild-type aSyn-mediated neurotoxicity in neuronal cells as well as its specific driving role in PD pathogenesis has yet to be fully clarified.

Hit and go CAS9 delivered through a lentiviral based self-limiting circuit.

In vivo application of the CRISPR-Cas9 technology is still limited by unwanted Cas9 genomic cleavages. Long-term expression of Cas9 increases the number of genomic loci non-specifically cleaved by the nuclease. Here we develop a Self-Limiting Cas9 circuit for Enhanced Safety and specificity (SLiCES) which consists of an expression unit for Streptococcus pyogenes Cas9 (SpCas9), a self-targeting sgRNA and a second sgRNA targeting a chosen genomic locus.

Establishment of induced pluripotent stem cell (iPSC) line from an 8-year old female patient with ischemic Moyamoya disease.

Peripheral blood mononuclear cells (PBMCs) were collected from an 8-year old female patient affected by ischemic Moyamoya disease (MMD). Patient's PBMCs were reprogrammed using Sendai virus particles delivering the four Yamanaka factors. The footprint free hiPSC line expressed the major pluripotency markers and exhibited a normal karyotype.

The activation of M2 muscarinic receptor inhibits cell growth and survival in human glioblastoma cancer stem cells.

The involvement of muscarinic receptors in cancer has been reported. Recently we have demonstrated that the activation of M2 muscarinic receptors, through arecaidine propargyl ester, arrests cell proliferation and induces apoptosis in primary and established glioblastoma cell lines. Considering the inability of conventional drugs to completely counteract the growth of glioblastoma cancer stem cells (GSCs), we have investigated the effect produced by arecaidine on GSC growth and survival.

Neurodevelopmental origin and adult neurogenesis of the neuroendocrine hypothalamus.

The adult hypothalamus regulates many physiological functions and homeostatic loops, including growth, feeding and reproduction. In mammals, the hypothalamus derives from the ventral diencephalon where two distinct ventricular proliferative zones have been described. Although a set of transcription factors regulating the hypothalamic development has been identified, the exact molecular mechanisms that drive the differentiation of hypothalamic neural precursor cells (NPCs) toward specific neuroendocrine neuronal subtypes is yet not fully disclosed.

Establishment of a radial glia-like mouse fetal hypothalamic neural stem cell line (AC1) able to differentiate into neuroendocrine cells.

The present study describes the generation and the characterization of a stable cell line of neural stem cells derived from embryonic mouse hypothalamus. These cells (AC1) grow as an adherent culture in defined serum-free medium and express typical markers of neurogenic radial glia and of hypothalamic precursors. After prolonged expansion, AC1 cells may be efficiently induced to differentiate into neurons and astroglial cells in vitro and start to express some hormonal neuropeptides, like TRH, CRH, and POMC.