A5051809929- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Genetics and Neurodevelopmental Disorders
- Neurogenesis and neuroplasticity mechanisms
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Zebrafish Biomedical Research Applications
- Neurotransmitter Receptor Influence on Behavior
- Virus-based gene therapy research
- Primate Behavior and Ecology
- Gene expression and cancer classification
- Advanced Fluorescence Microscopy Techniques
- Olfactory and Sensory Function Studies
- Chromosomal and Genetic Variations
- Molecular Biology Techniques and Applications
- Photosynthetic Processes and Mechanisms
- Autism Spectrum Disorder Research
- Ion channel regulation and function
- Pluripotent Stem Cells Research
- Neuroscience and Neuropharmacology Research
McGovern Institute for Brain Research
2016-2025
Massachusetts Institute of Technology
2016-2025
Broad Institute
2016-2025
Institute of Cognitive and Brain Sciences
2022
Dimagi (United States)
2022
Harvard University
2021
Moscow Institute of Thermal Technology
2019
Chinese Academy of Sciences
2005-2012
Shanghai Institutes for Biological Sciences
2005-2009
Center for Excellence in Molecular Cell Science
2005-2009
The postsynaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (SHANK3) is critical for the development function of glutamatergic synapses. Disruption SHANK3-encoding gene has been strongly implicated as a monogenic cause autism, Shank3 mutant mice show repetitive grooming social interaction deficits. Although basal ganglia dysfunction proposed to underlie behaviors, few studies have provided direct evidence support this notion exact cellular mechanisms remain largely...
ABSTRACT Studying the function and dysfunction of complex biological systems necessitates comprehensive understanding individual cells. Advancements in three-dimensional (3D) tissue processing imaging modalities have enabled rapid visualization phenotyping cells their spatial context. However, system-wide interrogation within large intact remains challenging, low throughput, error-prone owing to lack robust labeling technologies. Here we introduce a rapid, versatile, scalable method, eFLASH,...
Abstract Divergence of cis- regulatory elements drives species-specific traits 1 , but how this manifests in the evolution neocortex at molecular and cellular level remains unclear. Here we investigated gene programs primary motor cortex human, macaque, marmoset mouse using single-cell multiomics assays, generating expression, chromatin accessibility, DNA methylome chromosomal conformation profiles from a total over 200,000 cells. From these data, show evidence that divergence transcription...
The mammalian brain is composed of many structures, each with its own ontogenetic and developmental history. We used single-nucleus RNA sequencing to sample over 2.4 million cells across 18 locations in the common marmoset, a New World monkey primed for genetic engineering, examined gene expression patterns cell types within structures. adult transcriptomic identity most neuronal shaped more by origin than neurotransmitter signaling repertoire. Quantitative mapping GABAergic single-molecule...
Understanding cellular architectures and their connectivity is essential for interrogating system function dysfunction. However, we lack technologies mapping the multiscale details of individual cells in human organ-scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, information from same brain. The includes three core elements: vibrating microtome ultraprecision slicing large-scale tissues without losing (MEGAtome), polymer hydrogel-based...
Intellectual disability is a common neurodevelopmental disorder characterized by impaired intellectual and adaptive functioning. Both environmental insults genetic defects contribute to the etiology of disability. Copy number variations SORBS2 have been linked However, neurobiological function in brain unknown. The gene encodes ArgBP2 (Arg/c-Abl kinase binding protein 2) non-neuronal tissues alternatively spliced encode nArgBP2 protein. We found colocalized with F-actin at dendritic spines...
In primates, high-acuity vision is mediated by the fovea, a small specialized central region of retina. The unique to anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, extent cellular similarity across foveas and molecular underpinnings foveal maturation remain unclear. Here, we used high-throughput single-cell RNA sequencing profile retinal cells common marmoset (
The centrosome is the major microtubule-organizing center in animal cells. Although cytoplasmic dynein regulator Nudel interacts with centrosomes, its role herein remains unclear. Here, we show that Cos7 cells a mother centriole protein rapid turnover independent of activity. During duplication, targets to new later than ninein but earlier dynactin. Its localization requires C-terminal region essential for associations dynein, dynactin, pericentriolar material (PCM)-1, pericentrin, and...
The microtubule-based motor cytoplasmic dynein/dynactin is a force generator at the kinetochore. It also transports proteins away from kinetochores to spindle poles. Regulation of such diverse functions, however, poorly understood. We have previously shown that Nudel critical for dynein-mediated protein transport, whereas mitosin, kinetochore binds Nudel, involved in retention against microtubule-dependent stripping. Here we demonstrate required robust localization localizes after nuclear...
ABSTRACT Primates and rodents, which descended from a common ancestor more than 90 million years ago, exhibit profound differences in behavior cognitive capacity. Modifications, specializations, innovations to brain cell types may have occurred along each lineage. We used Drop-seq profile RNA expression 184,000 individual telencephalic interneurons humans, macaques, marmosets, mice. Conserved interneuron varied significantly abundance between mice primates, but much modestly among primates....
Abstract CACNA1I , a schizophrenia risk gene, encodes subtype of voltage-gated T-type calcium channel Ca V 3.3. We previously reported that patient-derived missense de novo mutation (R1346H) impaired 3.3 function. Here, we generated 3.3-RH knock-in animals, along with mice lacking 3.3, to investigate the biological impact R1346H (RH) variation. found RH altered cellular excitability in thalamic reticular nucleus (TRN), where is abundantly expressed. Moreover, produced marked deficits sleep...
eMAP preserves epitopes by purely physical tissue-hydrogel hybridization in swellable tissue-gel networks.
Adhesion and detachment are coordinated critical steps during cell migration. Conceptually, efficient migration requires both effective stabilization of membrane protrusions at the leading edge via nascent adhesions their successful persistence retraction trailing side disruption focal adhesions. As much smaller in size than adhesions, they expected to exhibit a stronger adhesivity order achieve coordination between front back. Here, we show that Nudel knockdown by interference RNA (RNAi)...
Deletion of the obsessive-compulsive disorder (OCD)-associated gene SAP90/PSD-95-associated protein 3 (Sapap3), which encodes a postsynaptic anchoring at corticostriatal synapses, causes OCD-like motor behaviors in mice. While synaptic dysfunction is central to this phenotype, striatum efficiently adapts pathological changes, often ways that expand upon original circuit impairment. Here, we show SAPAP3 deletion non-synaptic and pathway-specific alterations dorsolateral function. somatic...
Axonal transport is critical for neuronal function and survival. Cytoplasmic dynein its accessory complex dynactin form a microtubule minus end‐directed motor in charge of retrograde transport. In this study, we show that Nudel, regulator, was highly expressed dorsal root ganglion (DRG) neurons. Microinjection anti‐Nudel antibody into cultured DRG neurons abolished membranous organelles the axon led to dispersions Golgi cisternae soma. As result, lysosomes, which are normally enriched soma,...
Abstract Several computational methods have recently been developed for characterizing molecular tissue regions in spatially resolved transcriptomics (SRT) data. However, each method fundamentally relies on smoothing transcriptomic features across neighboring cells. Here, we demonstrate that increases autocorrelation between cells, causing latent space to encode physical adjacency rather than spatial patterns. We find randomly sub-sampling neighbors before mitigates autocorrelation,...