A5054787538- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Autism Spectrum Disorder Research
- Single-cell and spatial transcriptomics
- Cellular transport and secretion
- Chromosomal and Genetic Variations
- Virus-based gene therapy research
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Lipid Membrane Structure and Behavior
- Biomedical Ethics and Regulation
- Retinal Development and Disorders
University of Gothenburg
2024
Ollscoil na Gaillimhe – University of Galway
2019-2021
European Institute of Oncology
2018-2019
ABSTRACT The formation of mammalian synapses entails the precise alignment presynaptic release sites with postsynaptic receptors but how nascent cell–cell contacts translate into assembly specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that synapses, liprin-α proteins directly link trans -synaptic initial to downstream steps. Here show that, human neurons lacking all four isoforms, synaptic are formed recruitment active zone components and...
The regulation of the proliferation and polarity neural progenitors is crucial for development brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator both polarity, yet functional relevance its signaling unique features human corticogenesis remains to be elucidated. We harnessed cortical organoids probe longitudinal impact GSK3 inhibition through multiple developmental stages. Chronic increased caused massive derangement tissue architecture....
Abstract Presynaptic scaffold proteins, including liprin-α, RIM, and ELKS, are pivotal to the assembly of active zone regulating coupling calcium signals neurotransmitter release, yet underlying mechanism remains poorly understood. Here, we determined crystal structure liprin-α2/RIM1 complex, revealing a multifaceted intermolecular interaction that drives liprin-α/RIM assembly. Neurodevelopmental disease-associated mutations block formation complex. Disrupting this in neurons impairs...
Gene-edited human pluripotent stem cells provide attractive model systems to functionally interrogate the role of specific genetic variants in relevant cell types. However, need isolate and screen edited clones often remains a bottleneck, particular when recombination rates are sub-optimal. Here, we present protocol for flexible gene editing combining Cas9 ribonucleoprotein with donor templates delivered by adeno-associated virus (AAV) vectors yield high homologous recombination. To...
Summary The regulation of proliferation and polarity neural progenitors is crucial for the development brain cortex, with modes timings cell division intimately related to stereotypical acquisition layer-specific neuronal identities. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator both polarity, yet functional relevance its signaling unique features human corticogenesis remain be elucidated. Here we harness cortical organoids probe longitudinal impact...
NRXN1 copy number variation is a rare genetic factor commonly shared among autism spectrum disorder (ASD), schizophrenia, intellectual disability, epilepsy and developmental delay. Human induced pluripotent stem cells (iPSCs) are essential for disease modeling drug discovery, but familial cases particularly rare. We report here the derivation of iPSC lines from two controls three ASD patients carrying NRXN1α+/−, using non-integrating Sendai viral kit. The genotype karyotype resulting iPSCs...
Hundreds of rare risk factors have been identified for ASD, however, the underlying causes ~70% sporadic cases are unknown. Sporadic ASD models thus essential validating phenotypic commonality and drug suitability to majority patients. Here, we derived induced pluripotent stem cells (iPSCs) from one child paternal control, using non-integrating Sendai viral methods. The iPSCs strongly expressed pluripotency markers could be differentiated into three germ layers. Their normal karyotype was...
The induced pluripotent stem cell (iPSC) technology has offered an unprecedented opportunity for disease modelling and drug discovery. Here we used non-integrating Sendai viral method derived iPSCs from three young healthy Caucasian donors. All expressed pluripotency markers highly could be differentiated into germ lineages. They possess normal karyotype which was confirmed by whole genome SNP array. availability of the control offers phenotypic comparison editing a variety diseases.
NRXN1 encodes thousands of splicing variants categorized into long NRXN1α, short NRXN1β and extremely NRXN1γ, which exert differential roles in neuronal excitation/inhibition. NRXN1α deletions are common autism spectrum disorder (ASD) other neurodevelopmental/neuropsychiatric disorders. We derived induced pluripotent stem cells (iPSCs) from one sibling control two ASD probands carrying NRXN1α+/-, using non-integrating Sendai viral method. All iPSCs highly expressed pluripotency markers could...
NRXN1 deletions are commonly found in autism spectrum disorder (ASD) and other neurodevelopmental/neuropsychiatric disorders. Derivation of induced pluripotent stem cells (iPSCs) from different diseases involving deletion regions essential, as may produce thousands splicing variants. We report here the derivation iPSCs a sibling control an ASD proband carrying de novo heterozygous middle region NRXN1, using non-integrating Sendai viral kit. The genotype karyotype were validated by whole...