- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- Genetic Syndromes and Imprinting
- Neonatal Respiratory Health Research
- RNA Research and Splicing
- Birth, Development, and Health
- interferon and immune responses
- Tissue Engineering and Regenerative Medicine
- Genetics and Neurodevelopmental Disorders
- Proteoglycans and glycosaminoglycans research
- Private Equity and Venture Capital
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Prenatal Screening and Diagnostics
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Nuclear Receptors and Signaling
- Biomedical and Engineering Education
- Mitochondrial Function and Pathology
- CAR-T cell therapy research
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
- Clusterin in disease pathology
- Estrogen and related hormone effects
National Institute for Biological Standards and Control
2023
King's College London
2010-2021
Interferon-γ induces cellular and transcriptomic changes in human neural cells associated with neurodevelopmental disorders.
Abstract Neural induction is the first step in formation of vertebrate central nervous system. The emerging consensus mechanisms underling neural combined influences from inhibiting bone morphogenetic protein (BMP) signaling and activating fibroblast growth factor (FGF)/Erk signaling, which act extrinsically via either autocrine or paracrine fashions. However, do intrinsic forces (cues) exist they play decisive roles induction? These questions remain to be answered. Here, we have identified...
Our understanding of the molecular processes underlying Alzheimer's disease (AD) is still limited, hindering development effective treatments and highlighting need for human-specific models. Advances in identifying components amyloid cascade are progressing, including role protein clusterin mediating β-amyloid (Aβ) toxicity. Mutations gene (CLU), a major genetic AD risk factor, known to have important roles Aβ processing. Here we investigate how CLU mediates Aβ-driven neurodegeneration human...
Abstract Monoallelic gene expression, such as genomic imprinting, is well described. Less well-characterized are genes undergoing stochastic monoallelic expression (MA), where specific clones of cells express just one allele at a given locus. We performed genome-wide allelic assessment human clonal neural stem derived from cerebral cortex, striatum, and spinal cord, each with differing genotypes. assayed three separate lines donor, distinguishing MA genotypic effects. Roughly 2% showed...
Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that only present during earliest stages mammalian development. Epigenetic clocks utilize coordinated changes DNA methylation to make predictions correlate strongly with chronological age. It has been shown induction pluripotency rejuvenates...
Abstract Introduction The use of immortalized neural stem cells either as models development in vitro or cellular therapies central nervous system (CNS) disorders has been controversial. This controversy centered on the capacity to retain characteristic features progenitor resident tissue origin from which they were derived, and potential for tumorogenicity a result immortalization. Here, we report generation conditionally cell lines human fetal spinal cord tissue, addresses these issues....
Clonal level random allelic expression imbalance and monoallelic provides cellular heterogeneity within tissues by modulating dosage. Although such patterns have been observed in multiple cell types, little is known about when development these stochastic choices are made. We examine human neural progenitor cells before after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized (0.63% of expressed genes) generally reset a biallelic state pluripotent...
Hyaluronan (HA) is an extracellular glycosaminoglycan polysaccharide with widespread roles throughout development and in healthy neoplastic tissues. In pluripotent stem cell culture it can support both renewal differentiation. However, responses to HA are influenced by interaction a range of cognate factors receptors including components blood serum supplements, which alter results. These may contribute variation batch production yield phenotype as well heighten the risks adventitious...
Estrogens, in particular 17β-estradiol (estradiol) have repeatedly been shown to exert powerful influences over cognitive function, and particular, on a range of behaviours associated with neurodevelopmental disorders. This includes depressive anxious as well learning memory (including working memory). These enhancing effects be dependent increases the number dendritic spines alterations glutamate receptor transmission regulation synaptic protein expression. Modulation these functions can...
Abstract Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that only present during earliest stages mammalian development. Epigenetic clocks utilize coordinated changes DNA methylation to make predictions correlate strongly with chronological age. It has been shown induction pluripotency...
<title>Abstract</title> Background Hyaluronan (HA) is an extracellular glycosaminoglycan polysaccharide with widespread roles throughout development and in healthy neoplastic tissues. In pluripotent stem cell culture it can support both renewal differentiation. However, responses to HA are influenced by interaction a range of cognate factors receptors including components blood serum supplements, which alter results. These may contribute variation batch production yield phenotype as well...
Abstract Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-gamma (IFNγ), in offspring’s brains play a central role. IFNγ activates an antiviral cellular state, limiting viral entry and replication. In addition, has been implicated brain development. Here, we hypothesise that IFNγ-induced signalling contributes to molecular phenotypes associated with We find transient treatment neural progenitors derived from human induced...
Abstract Induced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that only present during early stages mammalian development. Epigenetic clocks utilize coordinated changes DNA methylation to make predictions correlate strongly with chronological age, has been shown induction pluripotency...