Michael Tieu
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View article: Multimodal Atlas of Caudate Head Reveals Impact of pTau Burden on Resident Glial Cells
Multimodal Atlas of Caudate Head Reveals Impact of pTau Burden on Resident Glial Cells Open
Background Dysfunction of the Basal Ganglia is implicated in several neurodegenerative diseases such as Parkinson’s and Huntington’s. A substructure of the Basal Ganglia, the caudate nucleus, is observed to have diffuse amyloid plaques in …
View article: An integrated, multiregional, and multimodal cell atlas of Alzheimer’s disease
An integrated, multiregional, and multimodal cell atlas of Alzheimer’s disease Open
Background Alzheimer’s disease (AD) is clinically characterized by a progressive cognitive decline associated with stereotyped accumulation of amyloid‐beta (Aβ) plaques and hyperphosphorylated Tau (pTau) tangles across brain regions. While…
View article: Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species
Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species Open
Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have also …
View article: Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species
Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species Open
Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have also …
View article: Distinctive physiology of molecularly identified medium spiny neurons in the macaque putamen
Distinctive physiology of molecularly identified medium spiny neurons in the macaque putamen Open
The distinctive physiology of striatal medium spiny neurons (MSNs) underlies their ability to integrate sensory and motor input. In rodents, MSNs have a hyperpolarized resting potential and low input resistance. When activated, they have a…
View article: Integrated multimodal cell atlas of Alzheimer’s disease
Integrated multimodal cell atlas of Alzheimer’s disease Open
Alzheimer’s disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomi…
View article: Areal specializations in the morpho-electric and transcriptomic properties of primate layer 5 extratelencephalic projection neurons
Areal specializations in the morpho-electric and transcriptomic properties of primate layer 5 extratelencephalic projection neurons Open
Large-scale analysis of single-cell gene expression has revealed transcriptomically defined cell subclasses present throughout the primate neocortex with gene expression profiles that differ depending upon neocortical region. Here, we test…
View article: A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types
A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types Open
Summary The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in healt…
View article: A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain Open
The mammalian brain consists of millions to billions of cells that are organized into many cell types with specific spatial distribution patterns and structural and functional properties 1–3 . Here we report a comprehensive and high-resolu…
View article: Connecting single-cell transcriptomes to projectomes in mouse visual cortex
Connecting single-cell transcriptomes to projectomes in mouse visual cortex Open
The mammalian brain is composed of diverse neuron types that play different functional roles. Recent single-cell RNA sequencing approaches have led to a whole brain taxonomy of transcriptomically-defined cell types, yet cell type definitio…
View article: Transcriptomic cytoarchitecture reveals principles of human neocortex organization
Transcriptomic cytoarchitecture reveals principles of human neocortex organization Open
Variation in cytoarchitecture is the basis for the histological definition of cortical areas. We used single cell transcriptomics and performed cellular characterization of the human cortex to better understand cortical areal specializatio…
View article: Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex
Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex Open
Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid–producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling pl…
View article: Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex
Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex Open
Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by disti…
View article: Comparative transcriptomics reveals human-specific cortical features
Comparative transcriptomics reveals human-specific cortical features Open
The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) f…
View article: Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species
Enhancer-AAVs allow genetic access to oligodendrocytes and diverse populations of astrocytes across species Open
Proper brain function requires the assembly and function of diverse populations of neurons and glia. Single cell gene expression studies have mostly focused on characterization of neuronal cell diversity; however, recent studies have also …
View article: Integrated multimodal cell atlas of Alzheimer’s disease
Integrated multimodal cell atlas of Alzheimer’s disease Open
Alzheimer’s disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive and stereotyped accumulation of protein aggregates, but the underlying molecular and cellu…
View article: A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain Open
The mammalian brain is composed of millions to billions of cells that are organized into numerous cell types with specific spatial distribution patterns and structural and functional properties. An essential step towards understanding brai…
View article: Signature morpho-electric properties of diverse GABAergic interneurons in the human neocortex
Signature morpho-electric properties of diverse GABAergic interneurons in the human neocortex Open
Human cortical interneurons have been challenging to study due to high diversity and lack of mature brain tissue platforms and genetic targeting tools. We employed rapid GABAergic neuron viral labeling plus unbiased Patch-seq sampling in b…
View article: Transcriptomic cytoarchitecture reveals principles of human neocortex organization
Transcriptomic cytoarchitecture reveals principles of human neocortex organization Open
Variation in cortical cytoarchitecture is the basis for histology-based definition of cortical areas, such as Brodmann areas. Single cell transcriptomics enables higher-resolution characterization of cell types in human cortex, which we us…
View article: Morpho-electric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex
Morpho-electric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex Open
Neocortical layer 1 (L1) is a site of convergence between pyramidal neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by disti…
View article: Comparative transcriptomics reveals human-specific cortical features
Comparative transcriptomics reveals human-specific cortical features Open
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, gorill…
View article: Local connectivity and synaptic dynamics in mouse and human neocortex
Local connectivity and synaptic dynamics in mouse and human neocortex Open
We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and h…
View article: A multimodal cell census and atlas of the mammalian primary motor cortex
A multimodal cell census and atlas of the mammalian primary motor cortex Open
Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of …
View article: Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse
Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse Open
The primary motor cortex (M1) is essential for voluntary fine motor control and is functionally conserved across mammals. Using high-throughput transcriptomic and epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey…