A5083066733- Pluripotent Stem Cells Research
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Cancer-related molecular mechanisms research
- Extracellular vesicles in disease
- RNA Interference and Gene Delivery
- Connexins and lens biology
- Yersinia bacterium, plague, ectoparasites research
- Adenosine and Purinergic Signaling
- Nicotinic Acetylcholine Receptors Study
- MicroRNA in disease regulation
- Neuroscience and Neural Engineering
- Virus-based gene therapy research
- Genetics and Neurodevelopmental Disorders
- Developmental Biology and Gene Regulation
- Cellular transport and secretion
- Ferroptosis and cancer prognosis
- Nerve injury and regeneration
- Retinal Development and Disorders
- Signaling Pathways in Disease
- Congenital heart defects research
University of Toronto
2020-2024
Sunnybrook Health Science Centre
2020-2024
Sunnybrook Research Institute
2020-2024
Canada Research Chairs
2021-2024
University of New Brunswick
2024
Sunnybrook Hospital
2020-2024
Indian Institute of Science Education and Research Kolkata
2020
Abstract Direct neuronal reprogramming is a promising approach to regenerate neurons from local glial cells. However, mechanisms of epigenome remodeling and co-factors facilitating this process are unclear. In study, we combined single-cell multiomics with genome-wide profiling three-dimensional nuclear architecture DNA methylation in mouse astrocyte-to-neuron mediated by Neurogenin2 (Ngn2) its phosphorylation-resistant form (PmutNgn2), respectively. We show that Ngn2 drives multilayered...
The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of adhesion molecules Wnt proteins. Single-cell transcriptomics double-mutant analyses revealed Pten Down syndrome molecule Dscam) are co-expressed function additively pattern mosaics. Mechanistically, loss accelerates endocytic...
Direct neuronal reprogramming, the process whereby a terminally differentiated cell is converted into an induced neuron without traversing pluripotent state, has tremendous therapeutic potential for host of neurodegenerative diseases. While there strong evidence astrocyte-to-neuron conversion
Altered expression and function of astroglial gap junction protein connexin 43 (Cx43) has increasingly been associated to neurotoxicity in Alzheimer disease (AD). Although earlier studies have examined the effect increased β-amyloid (Aβ) on Cx43 leading neuronal damage, underlying mechanisms by which Aβ modulates astrocytes remain elusive. Here, using mouse primary astrocyte cultures, we cellular processes can alter junctions. We show that Aβ25-35 impairs functional coupling yet increases...
ABSTRACT Unique hallmarks of human neocortical development include slower rates neurogenesis and the establishment an extracellular matrix-rich, outer-subventricular zone that supports basal neural progenitor cell expansion. How gene regulatory networks have evolved to support these human-specific neurodevelopmental features is poorly understood. Mining single data from cerebral organoids fetal cortices, we found NEUROG2 expression enriched in cells. To identify purify -expressing cells...
Proneural genes are conserved drivers of neurogenesis across the animal kingdom. How their functions have adapted to guide human-specific neurodevelopmental features is poorly understood. Here, we mined transcriptomic data from human fetal cortices and generated embryonic stem cell (hESC)-derived cortical organoids (COs) show that NEUROG1 NEUROG2 most highly expressed in basal neural progenitor cells, with pseudotime trajectory analyses indicating NEUROG1-derived lineages predominate early...
ABSTRACT Neocortical neural progenitor cells (NPCs) are molecularly heterogeneous, yet the genes that confer distinct neuronal morphologies and connectivities during development poorly understood. Here, we determined a proneural gene combinatorial code diversifies cortical NPCs. By mining scRNA-seq data from murine embryonic early postnatal cortices generating trajectory inference models, found Neurog2 is predominant, transiently co-expressed with Ascl1 and/or Neurog1 an apical-to-basal NPC...
ABSTRACT Schwann cells are the principal glial of peripheral nervous system, and their development into myelinating glia is critically dependent on MEK/ERK signaling. Ets-domain transcription factors ( Etv1, Etv4, Etv5 ) common downstream effectors signalling, but so far, only Etv1 has been ascribed a role in cell development, non-myelinating cells. Here, we examined , which expressed precursors, including neural crest satellite glia, lineage development. We analysed tm1Kmm mutants...
Abstract Isocitrate dehydrogenase (IDH) mutant gliomas, including oligodendroglioma (IDH-O) and astrocytoma (IDH-A), have signature slow-growth rates that are poorly understood. Here, we reveal SMPD3, a ceramide-producing sphingomyelinase implicated as tumor suppressor gene involved in extracellular vesicle biogenesis, suppresses IDH-mutant growth via autocrine paracrine actions. In patients with higher SMPD3 expression levels correlate longer survival, consistent ceramide acting an...
Abstract Oligodendrogliomas are lower-grade, slow-growing gliomas that ultimately fatal. Although driver mutations known, the mechanisms underlying their signature slow growth rates poorly understood. We found evidence for intra-tumoral interactions between neoplastic and non-neoplastic cells in oligodendroglioma tissues. To further study these cell interactions, we used two patient-derived lines of lower higher aggressivity. Both released extracellular vesicles had cytotoxic effects on...