A5019028054- RNA Research and Splicing
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Genetic Syndromes and Imprinting
- Epigenetics and DNA Methylation
- Connective tissue disorders research
- Neurogenesis and neuroplasticity mechanisms
- Axon Guidance and Neuronal Signaling
- RNA regulation and disease
- Plant Molecular Biology Research
- TGF-β signaling in diseases
- Electrohydrodynamics and Fluid Dynamics
- Tissue Engineering and Regenerative Medicine
- Genetics, Aging, and Longevity in Model Organisms
- Bone fractures and treatments
- Diabetes Treatment and Management
- Chromosomal and Genetic Variations
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Genetics and Neurodevelopmental Disorders
- Cancer-related molecular mechanisms research
- Micro and Nano Robotics
- Neuroscience and Neural Engineering
The Francis Crick Institute
2020-2025
Research Network (United States)
2025
University of Nottingham
2014-2020
University of Trento
2017-2020
Indiana University School of Medicine
2015
Park University
2015
During brain wiring, cue-induced axon behaviors such as directional steering and branching are aided by localized mRNA translation. Different guidance cues elicit translation of subsets mRNAs that differentially regulate the cytoskeleton, yet little is understood about how specific selected for MicroRNAs (miRNAs) critical translational regulators act through a sequence-specific mechanism. Here, we investigate local role miRNAs in mRNA-specific during pathfinding Xenopus laevis retinal...
Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA activate gene expression, though mechanisms through which pioneer remodel chromatin remain unclear. Here, using single-cell transcriptomics, we show that endogenous expression of neurogenic factor ASCL1, considered a classical factor, defines transient population progenitors human neural differentiation. Testing ASCL1's function knockout model define the unbound state, found...
5-Methylcytosine (5mC) is an epigenetic modification involved in regulation of gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC 5caC can be excised from DNA by thymine-DNA glycosylase (TDG) followed regeneration unmodified cytosine via the base excision repair pathway. Despite evidence that this mechanism operative embryonic stem cells, role TDG-dependent demethylation...
Article19 February 2020Open Access Source DataTransparent process Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits Eloina Corradi Department Cellular, Computational Integrative Biology - CIBIO, University Trento, Italy Search for more papers by this author Irene Dalla Costa Antoneta Gavoci Archana Iyer Michela Roccuzzo Tegan A Otto Eleonora Oliani Simone Bridi Stephanie Strohbuecker Gabriela Santos-Rodriguez Unidad de Genómica Avanzada...
Abstract Mutations in the SNCA gene cause autosomal dominant Parkinson’s disease (PD), with loss of dopaminergic neurons substantia nigra, and aggregation α-synuclein. The sequence molecular events that proceed from an mutation during development, to end-stage pathology is unknown. Utilising human-induced pluripotent stem cells (hiPSCs), we resolved temporal SNCA- induced pathophysiological order discover early, likely causative, events. Our small molecule-based protocol generates highly...
The evolution of established cancers is driven by selection cells with enhanced fitness. Subclonal mutations in numerous epigenetic regulator genes are common across cancer types, yet their functional impact has been unclear. Here, we show that disruption the regulatory network increases tolerance to unfavorable environments experienced within growing tumors promoting emergence stress-resistant subpopulations. Disruption control does not promote genetically defined subclones or favor a...
Shprintzen–Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap Marfan and Loeys–Dietz syndromes. These syndromes have commonly been associated enhanced TGF-β signaling. In SGS patients, heterozygous point mutations mapped to the transcriptional co-repressor SKI, which negative regulator of signaling that rapidly degraded upon ligand stimulation. The molecular consequences these mutations, however, are not understood. Here we use...
SOX1 is a member of the SOXB1 subgroup transcription factors involved in early embryogenesis, CNS development and maintenance neural stem cells. The structure regulation human locus has been less studied than that SOX2, another for which an overlapping transcript reported. Here we report harbours (SOX1-OT), describe expression, splicing variants detection SOX1-OT different cancer RT-PCR RACE experiments were performed to detect characterise neuroprogenitor cultures across cell lines. was...
RNA editing is a posttranscriptional mechanism that targets changes in transcripts to modulate innate immune responses. We report the role of astrocyte-specific, ADAR1-mediated neuroinflammation Parkinson’s disease (PD). generated human induced pluripotent stem cell–derived astrocytes, neurons and cocultures exposed them small soluble alpha-synuclein aggregates. Oligomeric triggered an inflammatory glial state associated with Toll-like receptor activation, viral responses, cytokine...
Raman micro-spectroscopy (RMS) is a non-invasive technique for imaging live cells <italic>in vitro</italic>. However, obtaining quantitative molecular information from spectra difficult because the intensity of band proportional to number molecules in sampled volume, which depends on local concentration and thickness cell. In order understand these effects, we combined RMS with atomic force microscopy (AFM), that can measure accurately profile cells. Solution-based calibration models RNA...
Bone marrow-derived mesenchymal stem cells (MSCs) are widely used as a cellular model of bone formation, and can mineralize in vitro response to osteogenic medium (OM). It is unclear, however, whether this property specific origin. We analysed the OM 3 non-osteogenic lines, HEK293, HeLa NTera, compared MSCs. Whereas HEK293 failed respond conditions, 2 carcinoma-derived lines NTera deposited calcium phosphate mineral comparable that present MSC cultures. However, unlike MSCs, cultures did so...
Abstract Naïve pluripotency is a transient state during mammalian development that can be recapitulated indefinitely in vitro by inhibition of the mitogen-activated protein kinase (MAPK/Erk) signalling and activation STAT Wnt pathways. How Erk inhibited vivo to promote naïve remains largely unknown. By combining live cell imaging quantitative proteomics we found FGF2, known activator pro-differentiation cue, induces instead long-term both ES cells mouse embryos. We show results from...
Abstract RNA editing is a post transcriptional mechanism that targets changes in transcripts to modulate innate immune responses. We report the role of astrocyte specific, ADAR1 mediated neuroinflammation Parkinson’s disease. generated hiPSC-derived astrocytes, neurons and co-cultures exposed them small soluble alpha-synuclein aggregates. Oligomeric triggered an inflammatory glial state associated with TLR activation, viral responses, cytokine secretion. This reactive resulted loss...
Abstract Neuronal insulin resistance is linked to the pathogenesis of Parkinson’s disease through unclear, but potentially targetable, mechanisms. We delineated neuronal and glial mechanisms glucagon-like 1 peptide (GLP-1) receptor agonism in human iPSC models synucleinopathy, corroborated our findings patient samples from a Phase 2 trial GLP-1R agonist ( NCT01971242 ). Human synucleinopathy exhibit dysfunctional signalling, which associated with inhibition neuroprotective Akt pathways,...
Stem cells are increasingly seen as a solution for many health challenges an ageing population. However, their potential benefits in the clinic currently curtailed by technical such high cell dose requirements and point of care delivery, which pose sourcing logistics challenges. Cell manufacturing solutions development to address supply issue, ancillary technologies nanoparticle-based labelling being developed improve stem delivery enable post-treatment follow-up. The application magnetic...
Quiescence is a cellular state characterised by reversible cell-cycle arrest and diminished biosynthetic activity that protects against environmental insults, replicative exhaustion proliferation-induced mutations 1 . Entry into exit from this controls development, maintenance repair of tissues plus, in the adult central nervous system, generation new neurons thus cognition mood 2–4 Cancer stem cells too can undergo quiescence, which confers them resistance to current therapies 5, 6 Despite...
The transcription factor SOX1 is a key regulator of neural stem cell development, acting to keep cells (NSCs) in an undifferentiated state. Postnatal expression Sox1 typically confined the central nervous system (CNS), however, its non-neural tissues has recently been implicated tumorigenesis. mechanism through which may exert function not fully understood, and studies have mainly focused on changes at transcriptional level, while post-translational regulation remains undetermined. To...
Abstract Various species of non-coding RNAs (ncRNAs) are enriched in subcellular compartments but the mechanisms orchestrating their delocalization and local functions remain largely unknown. We investigated both aspects using elongating retinal ganglion cell axon its tip, growth cone, as models. reveal that specific endogenous precursor microRNAs (pre-miRNAs) actively trafficked, anchored to CD63-positive vesicles, distal axons along microtubules. Upon exposure chemotropic cue Sema3A,...
A bstract Pioneer transcription factors are thought to play pivotal roles in developmental processes by binding nucleosomal DNA activate gene expression. The role of neurogenic pioneer factor ASCL1 shaping chromatin landscape human neurogenesis remains unclear. Here we show that acts as a transient population progenitors. Using an vitro knockout model it drives progenitor differentiation cis-regulation both classical and non-pioneer remodeler, where binds permissive induce conformation...
Sex chromosomes are emerging as key regulators of adult health and disease in males (XY) females (XX), but their impact on embryo development is poorly understood. Using single-cell RNA sequencing (scRNA-seq) wild type aneuploid mouse embryos, we show that sex significantly shape the preimplantation transcriptional landscape. A hierarchy effects identified, distinctly mediated by Y chromosome, dosage X chromosomes, X-chromosome imprinting, Xist, non-coding initiates X-inactivation. The have...
ABSTRACT Shprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated enhanced TGF-β signaling. In SGS patients, heterozygous point mutations mapped to the transcriptional corepressor SKI, which negative regulator of signaling that rapidly degraded upon ligand stimulation. The molecular consequences these mutations, however, are not understood. Here we use...