A5084408069- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Congenital heart defects research
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- Mosquito-borne diseases and control
- Cancer-related molecular mechanisms research
- Genetic Associations and Epidemiology
- Ion channel regulation and function
- Axon Guidance and Neuronal Signaling
- Autism Spectrum Disorder Research
- Animal Genetics and Reproduction
- Bioinformatics and Genomic Networks
- Fibroblast Growth Factor Research
- Stress Responses and Cortisol
- Neonatal Respiratory Health Research
- Health, Environment, Cognitive Aging
- Virology and Viral Diseases
- Hearing, Cochlea, Tinnitus, Genetics
- HIV Research and Treatment
Yale University
2015-2025
Kavli Institute for Theoretical Sciences
2019
University of Chicago
2008-2014
Case Western Reserve University
2003-2006
University Hospitals of Cleveland
2003
George Washington University
2003
National Cancer Institute
2003
Center for Cancer Research
2003
INTRODUCTION The brain is responsible for cognition, behavior, and much of what makes us uniquely human. development the a highly complex process, this process reliant on precise regulation molecular cellular events grounded in spatiotemporal transcriptome. Disruption can lead to neuropsychiatric disorders. RATIONALE regulatory, epigenomic, transcriptomic features human have not been comprehensively compiled across time, regions, or cell types. Understanding etiology disorders requires...
INTRODUCTION Improved understanding of how the developing human nervous system differs from that closely related nonhuman primates is fundamental for teasing out human-specific aspects behavior, cognition, and disorders. RATIONALE The shared unique functional properties are rooted in complex transcriptional programs governing development distinct cell types, neural circuits, regions. However, precise molecular mechanisms underlying features have been only minimally characterized. RESULTS We...
The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation characterization, including single-cell RNA-seq, of neocortical spinal cord neuroepithelial stem (NES) cells to model early human ZIKV-related neuropathogenesis. By analyzing NES cells, organotypic fetal brain slices, a ZIKV-infected micrencephalic brain, show that ZIKV infects both as well their homolog, radial glial (RGCs), causing...
The makings of the primate brain Although nonhuman brains are similar to our own, disparity between their and cognitive abilities tells us that surface similarity is not whole story. Sousa et al. overlaid transcriptome histological analyses see what makes human different from those primates. Various differentially expressed genes, such as encoding transcription factors, could alter transcriptional programs. Others were associated with neuromodulatory systems. Furthermore, dopaminergic...
Langerhans cells (LCs) are suspected to be initial targets for HIV after sexual exposure (by becoming infected or by capturing virus). Here, productive R5 infection of LC ex vivo and LC-mediated transmission virus CD4 + T were both found depend on CCR5. By contrast, monocyte-derived dendritic transfer from mediated CCR5-dependent as well DC-specific ICAM-3-grabbing nonintegrin-dependent pathways. Furthermore, in 62 healthy individuals, levels LCs associated with CCR5 genotype. Specifically,...
Gene expression levels vary across developmental stage, cell type, and region in the brain. Genomic variants also contribute to variation expression, some neuropsychiatric disorder loci may exert their effects through this mechanism. To investigate these relationships, we present BrainVar, a unique resource of paired whole-genome bulk tissue RNA sequencing from dorsolateral prefrontal cortex 176 individuals prenatal postnatal development. Here identify common that alter gene (expression...
Abstract The ventrolateral pallial (VLp) excitatory neurons in the claustro-amygdalar complex and piriform cortex (PIR; which forms part of palaeocortex) form reciprocal connections with prefrontal (PFC), integrating cognitive sensory information that results adaptive behaviours 1–5 . Early-life disruptions these circuits are linked to neuropsychiatric disorders 4–8 , highlighting importance understanding their development. Here we reveal transcription factors SOX4, SOX11 TFAP2D have a...
The cortical hem, a source of Wingless-related (WNT) and bone morphogenetic protein (BMP) signaling in the dorsomedial telencephalon, is embryonic organizer for hippocampus. Whether hem major regulator patterning outside hippocampus has not been investigated. We examined regional organization across entire cerebral cortex mice genetically engineered to lack hem. Indicating that regulates dorsoventral hemisphere, neocortex, particularly was reduced size late-stage hem-ablated embryos, whereas...
Genetic variants in the voltage-gated sodium channels SCN1A, SCN2A, SCN3A, and SCN8A are leading causes of epilepsy, developmental delay, autism spectrum disorder. The mRNA splicing patterns all four genes vary across development rodent brain, including mutually exclusive copies fifth protein-coding exon detected neonate (5N) adult (5A). A second pair exons is reported only (18N 18A). We aimed to quantify expression individual developing human brain. RNA-seq data from 783 brain samples were...
Mammals have evolved a plethora of adaptations that enabled them to thrive in diverse environments. Among the most significant is emergence more complex brain, exemplified by dramatic transformation dorsal cortex from single layer excitatory projection neurons (ExNs) ancestors multilayered cerebral neocortex enriched with intratelencephalic (IT) and extratelencephalic (ET) ExN subtypes. These ExNs established specialized systems, such as corticospinal tract corpus callosum, enhancing brain...
Abstract The ventropallial excitatory neurons (ExNs) in the claustro-amygdalar complex and piriform cortex (PIR; part of paleocortex) form crucial reciprocal connections with prefrontal (PFC), integrating cognitive sensory information that result adaptive behaviors. Early-life disruptions these circuits are linked to neuropsychiatric disorders, highlighting importance understanding their development. Our study uncovers transcription factors SOX4, SOX11, TFAP2D play a pivotal role...
ABSTRACT Cerebellar development and function require precise regulation of molecular cellular programs to coordinate motor functions integrate network signals required for cognition emotional regulation. However, understanding human cerebellar is limited. Here, we combined spatially resolved single-cell transcriptomics systematically map the molecular, cellular, spatial composition early mid-gestational cerebellum. This enabled us transcriptionally profile major cell types examine dynamics...
Summary Variation in gene expression underlies neurotypical development, while genomic variants contribute to neuropsychiatric disorders. BrainVar is a unique resource of paired whole-genome sequencing and bulk-tissue RNA-sequencing from the human dorsolateral prefrontal cortex 176 individuals across prenatal postnatal providing opportunity assay transcriptomic variation tandem. Leveraging this resource, we identified rare premature stop codons with commensurate reduced allele-specific...
Abstract Objective Genetic variants in the voltage-gated sodium channels SCN1A, SCN2A, SCN3A, and SCN8A are leading causes of epilepsy, developmental delay, autism spectrum disorder. The mRNA splicing patterns all four genes vary across development rodent brain, including mutually exclusive copies fifth protein-coding exon detected neonate (5N) adult (5A). A second pair exons is reported only (18N 18A). We aimed to quantify expression individual developing human neocortex. Methods RNA-seq...