Saroja Somasundaram
A5047484422- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Bioinformatics and Genomic Networks
- Cell Image Analysis Techniques
- Neural dynamics and brain function
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Gene Regulatory Network Analysis
- RNA Interference and Gene Delivery
- RNA regulation and disease
- 3D Printing in Biomedical Research
- Glycosylation and Glycoproteins Research
- Gene expression and cancer classification
- Virus-based gene therapy research
- Microbial Metabolic Engineering and Bioproduction
- Genetic Neurodegenerative Diseases
- Machine Learning in Bioinformatics
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Protein Structure and Dynamics
Allen Institute
2018-2024
Allen Institute for Brain Science
2018-2024
Seattle University
2022
Northeastern University
2015
Abstract The primary motor cortex (M1) is essential for voluntary fine-motor control and functionally conserved across mammals 1 . Here, using high-throughput transcriptomic epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys mice, we demonstrate a broadly cellular makeup this region, with similarities that mirror evolutionary distance are consistent between the transcriptome epigenome. core molecular identities neuronal non-neuronal cell types allow us to...
Viral genetic tools that target specific brain cell types could transform basic neuroscience and targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome control expression in adeno-associated virus (AAV) vectors. The cellular specificity reporter enhancer-AAVs is established by molecular profiling after systemic AAV delivery mouse. Over 30% produce subclass, including both...
Variation in cytoarchitecture is the basis for histological definition of cortical areas. We used single cell transcriptomics and performed cellular characterization human cortex to better understand areal specialization. Single-nucleus RNA-sequencing 8 areas spanning structural variation showed a highly consistent makeup 24 subclasses. However, proportions excitatory neuron subclasses varied substantially, likely reflecting differences connectivity across primary sensorimotor association...
The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates poorly understood. We used comparative single-nucleus transcriptomics to analyze samples the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, common marmosets understand human-specific features neocortex. Human, chimpanzee, gorilla MTG showed highly similar cell-type composition laminar organization as well a large shift in proportions deep-layer...
Abstract The primary motor cortex (M1) is essential for voluntary fine control and functionally conserved across mammals. Using high-throughput transcriptomic epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey, mouse, we demonstrate a broadly cellular makeup this region, whose similarity mirrors evolutionary distance consistent between the transcriptome epigenome. core molecular identity neuronal non-neuronal types allowed generation cross-species consensus cell...
Single-cell transcriptomic studies have identified a conserved set of neocortical cell types from small postmortem cohorts. We extended these efforts by assessing type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one 125 robust in the middle temporal gyrus. However, we found interindividual variance abundances gene expression signatures, particularly deep-layer glutamatergic neurons microglia. A minority donor is explainable age,...
The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution each cell type processes guided by essential for understanding its function in health and disease. We used transcriptomic epigenomic cortical taxonomies from mouse human define marker genes putative enhancers created a large toolkit transgenic lines enhancer AAVs selective targeting populations. report evaluation fifteen new driver lines, two reporter >800 different...
Abstract Elucidating the cellular architecture of human neocortex is central to understanding our cognitive abilities and susceptibility disease. Here we applied single nucleus RNA-sequencing perform a comprehensive analysis cell types in middle temporal gyrus cerebral cortex. We identify highly diverse set excitatory inhibitory neuronal that are mostly sparse, with being less layer-restricted than expected. Comparison similar mouse cortex dataset revealed surprisingly well-conserved enables...
Abstract Humans have unique cognitive abilities among primates, including language, but their molecular, cellular, and circuit substrates are poorly understood. We used comparative single nucleus transcriptomics in adult humans, chimpanzees, gorillas, rhesus macaques, common marmosets from the middle temporal gyrus (MTG) to understand human-specific features of cellular molecular organization. Human, chimpanzee, gorilla MTG showed highly similar cell type composition laminar organization, a...
Summary Viral genetic tools to target specific brain cell types in humans and non-genetic model organisms will transform basic neuroscience targeted gene therapy. Here we used comparative epigenetics identify thousands of human neuronal subclass-specific putative enhancers regulate viral tools, 34% these were conserved mouse. We established an AAV platform evaluate cellular specificity functional by multiplexed fluorescent situ hybridization (FISH) single RNA sequencing. Initial testing...
Abstract Variation in cortical cytoarchitecture is the basis for histology-based definition of areas, such as Brodmann areas. Single cell transcriptomics enables higher-resolution characterization types human cortex, which we used to revisit idea canonical microcircuit and understand functional areal specialization. Deeply sampled single nucleus RNA-sequencing eight areas spanning structural variation showed highly consistent cellular makeup 24 coarse subclasses. However, proportions...
Identifying cell type-specific enhancers in the brain is critical to building genetic tools for investigating mammalian brain. Computational methods functional enhancer prediction have been proposed and validated fruit fly not yet We organized 'Brain Initiative Cell Census Network (BICCN) Challenge: Predicting Functional Type-Specific Enhancers from Cross-Species Multi-Omics' assess machine learning feature-based designed nominate DNA sequences target types mouse cortex. Methods were...
Viral genetic tools to target specific brain cell types in humans and nongenetic model organisms will transform basic neuroscience targeted gene therapy. Here we used comparative epigenetics identify thousands of human neuronal subclass-specific putative enhancers regulate viral tools, 34% these were conserved mouse. We established an AAV platform evaluate cellular specificity functional by multiplexed fluorescent situ hybridization (FISH) single RNA sequencing. Initial testing mouse...
Abstract Single cell transcriptomic studies have identified a conserved set of neocortical types from small post-mortem cohorts. We extend these efforts by assessing type variation across 75 adult individuals undergoing epilepsy and tumor surgeries. Nearly all nuclei map to one 125 robust in middle temporal gyrus, but with varied abundances gene expression signatures donors, particularly deep layer glutamatergic neurons. A minority variance is explainable known factors including donor...