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  1. Article ; Online: Measuring APP carboxy-terminal fragments.

    Esposito, Luke A

    Methods in molecular biology (Clifton, N.J.)

    2011  Volume 670, Page(s) 71–84

    Abstract: The accumulation of the amyloid-β (Aβ) peptide in the form of insoluble fibrillar deposits and soluble oligomeric aggregates is widely believed to play a causal role in Alzheimer's disease (AD). Proteolytic cleavage of APP by the β-site APP cleaving ... ...

    Abstract The accumulation of the amyloid-β (Aβ) peptide in the form of insoluble fibrillar deposits and soluble oligomeric aggregates is widely believed to play a causal role in Alzheimer's disease (AD). Proteolytic cleavage of APP by the β-site APP cleaving enzyme (BACE1) near the C-terminus results in the formation of the APP C-terminal fragment (CTF) C99, a substrate for subsequent cleavage by γ-secretase to generate Aβ. Alternatively, APP cleavage by α-secretase to generate the APP CTF C83 occurs within the Aβ region, precluding its formation. Therefore, modulation of β- and/or γ-secretase activity represents important therapeutic targets. Transgenic mice overexpressing human APP generate detectable levels of APP CTFs and Aβ. We have shown that highly sensitive and specific methods for determining levels of APP CTFs and Aβ are useful for understanding how genetic manipulation of APP processing impacts Aβ generation and accumulation.
    MeSH term(s) Alzheimer Disease/metabolism ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Blotting, Western ; Humans ; Mice ; Mice, Transgenic
    Chemical Substances Amyloid beta-Protein Precursor ; Amyloid Precursor Protein Secretases (EC 3.4.-)
    Language English
    Publishing date 2011
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-60761-744-0_6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Cell-type specific molecular signatures of aging revealed in a brain-wide transcriptomic cell-type atlas.

    Jin, Kelly / Yao, Zizhen / van Velthoven, Cindy T J / Kaplan, Eitan S / Glattfelder, Katie / Barlow, Samuel T / Boyer, Gabriella / Carey, Daniel / Casper, Tamara / Chakka, Anish Bhaswanth / Chakrabarty, Rushil / Clark, Michael / Departee, Max / Desierto, Marie / Gary, Amanda / Gloe, Jessica / Goldy, Jeff / Guilford, Nathan / Guzman, Junitta /
    Hirschstein, Daniel / Lee, Changkyu / Liang, Elizabeth / Pham, Trangthanh / Reding, Melissa / Ronellenfitch, Kara / Ruiz, Augustin / Sevigny, Josh / Shapovalova, Nadiya / Shulga, Lyudmila / Sulc, Josef / Torkelson, Amy / Tung, Herman / Levi, Boaz / Sunkin, Susan M / Dee, Nick / Esposito, Luke / Smith, Kimberly / Tasic, Bosiljka / Zeng, Hongkui

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Biological aging can be defined as a gradual loss of homeostasis across various aspects of molecular and cellular function. Aging is a complex and dynamic process which influences distinct cell types in a myriad of ways. The cellular architecture of the ... ...

    Abstract Biological aging can be defined as a gradual loss of homeostasis across various aspects of molecular and cellular function. Aging is a complex and dynamic process which influences distinct cell types in a myriad of ways. The cellular architecture of the mammalian brain is heterogeneous and diverse, making it challenging to identify precise areas and cell types of the brain that are more susceptible to aging than others. Here, we present a high-resolution single-cell RNA sequencing dataset containing ~1.2 million high-quality single-cell transcriptomic profiles of brain cells from young adult and aged mice across both sexes, including areas spanning the forebrain, midbrain, and hindbrain. We find age-associated gene expression signatures across nearly all 130+ neuronal and non-neuronal cell subclasses we identified. We detect the greatest gene expression changes in non-neuronal cell types, suggesting that different cell types in the brain vary in their susceptibility to aging. We identify specific, age-enriched clusters within specific glial, vascular, and immune cell types from both cortical and subcortical regions of the brain, and specific gene expression changes associated with cell senescence, inflammation, decrease in new myelination, and decreased vasculature integrity. We also identify genes with expression changes across multiple cell subclasses, pointing to certain mechanisms of aging that may occur across wide regions or broad cell types of the brain. Finally, we discover the greatest gene expression changes in cell types localized to the third ventricle of the hypothalamus, including tanycytes, ependymal cells, and
    Language English
    Publishing date 2023-07-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.26.550355
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Early induction of oxidative stress in mouse model of Alzheimer disease with reduced mitochondrial superoxide dismutase activity.

    Lee, Hyun-Pil / Pancholi, Neel / Esposito, Luke / Previll, Laura A / Wang, Xinglong / Zhu, Xiongwei / Smith, Mark A / Lee, Hyoung-gon

    PloS one

    2012  Volume 7, Issue 1, Page(s) e28033

    Abstract: While oxidative stress has been linked to Alzheimer's disease, the underlying pathophysiological relationship is unclear. To examine this relationship, we induced oxidative stress through the genetic ablation of one copy of mitochondrial antioxidant ... ...

    Abstract While oxidative stress has been linked to Alzheimer's disease, the underlying pathophysiological relationship is unclear. To examine this relationship, we induced oxidative stress through the genetic ablation of one copy of mitochondrial antioxidant superoxide dismutase 2 (Sod2) allele in mutant human amyloid precursor protein (hAPP) transgenic mice. The brains of young (5-7 months of age) and old (25-30 months of age) mice with the four genotypes, wild-type (Sod2(+/+)), hemizygous Sod2 (Sod2(+/-)), hAPP/wild-type (Sod2(+/+)), and hAPP/hemizygous (Sod2(+/-)) were examined to assess levels of oxidative stress markers 4-hydroxy-2-nonenal and heme oxygenase-1. Sod2 reduction in young hAPP mice resulted in significantly increased oxidative stress in the pyramidal neurons of the hippocampus. Interestingly, while differences resulting from hAPP expression or Sod2 reduction were not apparent in the neurons in old mice, oxidative stress was increased in astrocytes in old, but not young hAPP mice with either Sod2(+/+) or Sod2(+/-). Our study shows the specific changes in oxidative stress and the causal relationship with the pathological progression of these mice. These results suggest that the early neuronal susceptibility to oxidative stress in the hAPP/Sod2(+/-) mice may contribute to the pathological and behavioral changes seen in this animal model.
    MeSH term(s) Aldehydes/metabolism ; Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Heme Oxygenase-1/metabolism ; Humans ; Mice ; Mice, Transgenic ; Mitochondria/enzymology ; Mitochondria/metabolism ; Oxidative Stress/genetics ; Oxidative Stress/physiology ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism
    Chemical Substances Aldehydes ; Amyloid beta-Protein Precursor ; Heme Oxygenase-1 (EC 1.14.14.18) ; Superoxide Dismutase (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1) ; 4-hydroxy-2-nonenal (K1CVM13F96)
    Language English
    Publishing date 2012-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0028033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain.

    Yao, Zizhen / van Velthoven, Cindy T J / Kunst, Michael / Zhang, Meng / McMillen, Delissa / Lee, Changkyu / Jung, Won / Goldy, Jeff / Abdelhak, Aliya / Baker, Pamela / Barkan, Eliza / Bertagnolli, Darren / Campos, Jazmin / Carey, Daniel / Casper, Tamara / Chakka, Anish Bhaswanth / Chakrabarty, Rushil / Chavan, Sakshi / Chen, Min /
    Clark, Michael / Close, Jennie / Crichton, Kirsten / Daniel, Scott / Dolbeare, Tim / Ellingwood, Lauren / Gee, James / Glandon, Alexandra / Gloe, Jessica / Gould, Joshua / Gray, James / Guilford, Nathan / Guzman, Junitta / Hirschstein, Daniel / Ho, Windy / Jin, Kelly / Kroll, Matthew / Lathia, Kanan / Leon, Arielle / Long, Brian / Maltzer, Zoe / Martin, Naomi / McCue, Rachel / Meyerdierks, Emma / Nguyen, Thuc Nghi / Pham, Trangthanh / Rimorin, Christine / Ruiz, Augustin / Shapovalova, Nadiya / Slaughterbeck, Cliff / Sulc, Josef / Tieu, Michael / Torkelson, Amy / Tung, Herman / Cuevas, Nasmil Valera / Wadhwani, Katherine / Ward, Katelyn / Levi, Boaz / Farrell, Colin / Thompson, Carol L / Mufti, Shoaib / Pagan, Chelsea M / Kruse, Lauren / Dee, Nick / Sunkin, Susan M / Esposito, Luke / Hawrylycz, Michael J / Waters, Jack / Ng, Lydia / Smith, Kimberly A / Tasic, Bosiljka / Zhuang, Xiaowei / Zeng, Hongkui

    bioRxiv : the preprint server for biology

    2023  

    Abstract: 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 brain function is ... ...

    Abstract 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 brain function is to obtain a parts list, i.e., a catalog of cell types, of the brain. Here, we report a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain. The cell type atlas was created based on the combination of two single-cell-level, whole-brain-scale datasets: a single-cell RNA-sequencing (scRNA-seq) dataset of ~7 million cells profiled, and a spatially resolved transcriptomic dataset of ~4.3 million cells using MERFISH. The atlas is hierarchically organized into five nested levels of classification: 7 divisions, 32 classes, 306 subclasses, 1,045 supertypes and 5,200 clusters. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The results reveal unique features of cell type organization in different brain regions, in particular, a dichotomy between the dorsal and ventral parts of the brain: the dorsal part contains relatively fewer yet highly divergent neuronal types, whereas the ventral part contains more numerous neuronal types that are more closely related to each other. We also systematically characterized cell-type specific expression of neurotransmitters, neuropeptides, and transcription factors. The study uncovered extraordinary diversity and heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types across the brain, suggesting they mediate a myriad of modes of intercellular communications. Finally, we found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. The whole-mouse-brain transcriptomic and spatial cell type atlas establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cell type and circuit function, development, and evolution of the mammalian brain.
    Language English
    Publishing date 2023-03-06
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.03.06.531121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Connecting single-cell transcriptomes to projectomes in mouse visual cortex.

    Sorensen, Staci A / Gouwens, Nathan W / Wang, Yun / Mallory, Matt / Budzillo, Agata / Dalley, Rachel / Lee, Brian / Gliko, Olga / Kuo, Hsien-Chi / Kuang, Xiuli / Mann, Rusty / Ahmadinia, Leila / Alfiler, Lauren / Baftizadeh, Fahimeh / Baker, Katherine / Bannick, Sarah / Bertagnolli, Darren / Bickley, Kris / Bohn, Phil /
    Brown, Dillan / Bomben, Jasmine / Brouner, Krissy / Chen, Chao / Chen, Kai / Chvilicek, Maggie / Collman, Forrest / Daigle, Tanya / Dawes, Tim / de Frates, Rebecca / Dee, Nick / DePartee, Maxwell / Egdorf, Tom / El-Hifnawi, Laila / Enstrom, Rachel / Esposito, Luke / Farrell, Colin / Gala, Rohan / Glomb, Andrew / Gamlin, Clare / Gary, Amanda / Goldy, Jeff / Gu, Hong / Hadley, Kristen / Hawrylycz, Mike / Henry, Alex / Hill, Dijon / Hirokawa, Karla E / Huang, Zili / Johnson, Katelyn / Juneau, Zoe / Kebede, Sara / Kim, Lisa / Lee, Changkyu / Lesnar, Phil / Li, Anan / Li, Yaoyao / Liang, Elizabeth / Link, Katie / Maxwell, Michelle / McGraw, Medea / McMillen, Delissa A / Mukora, Alice / Ng, Lindsay / Ochoa, Thomas / Oldre, Aaron / Park, Daniel / Pom, Christina Alice / Popovich, Zoran / Potekhina, Lydia / Rajanbabu, Ram / Ransford, Shea / Reding, Melissa / Ruiz, Augustin / Sandman, David / Siverts, La'Akea / Smith, Kimberly A / Stoecklin, Michelle / Sulc, Josef / Tieu, Michael / Ting, Jonathan / Trinh, Jessica / Vargas, Sara / Vumbaco, Dave / Walker, Miranda / Wang, Micheal / Wanner, Adrian / Waters, Jack / Williams, Grace / Wilson, Julia / Xiong, Wei / Lein, Ed / Berg, Jim / Kalmbach, Brian / Yao, Shenqin / Gong, Hui / Luo, Qingming / Ng, Lydia / Sümbül, Uygar / Jarsky, Tim / Yao, Zizhen / Tasic, Bosiljka / Zeng, Hongkui

    bioRxiv : the preprint server for biology

    2023  

    Abstract: 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 definitions that include ...

    Abstract 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 definitions that include multiple cellular properties can offer additional insights into a neuron's role in brain circuits. While the Patch-seq method can investigate how transcriptomic properties relate to the local morphological and electrophysiological properties of cell types, linking transcriptomic identities to long-range projections is a major unresolved challenge. To address this, we collected coordinated Patch-seq and whole brain morphology data sets of excitatory neurons in mouse visual cortex. From the Patch-seq data, we defined 16 integrated morpho-electric-transcriptomic (MET)-types; in parallel, we reconstructed the complete morphologies of 300 neurons. We unified the two data sets with a multi-step classifier, to integrate cell type assignments and interrogate cross-modality relationships. We find that transcriptomic variations within and across MET-types correspond with morphological and electrophysiological phenotypes. In addition, this variation, along with the anatomical location of the cell, can be used to predict the projection targets of individual neurons. We also shed new light on infragranular cell types and circuits, including cell-type-specific, interhemispheric projections. With this approach, we establish a comprehensive, integrated taxonomy of excitatory neuron types in mouse visual cortex and create a system for integrated, high-dimensional cell type classification that can be extended to the whole brain and potentially across species.
    Language English
    Publishing date 2023-11-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.25.568393
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Integrated multimodal cell atlas of Alzheimer's disease.

    Gabitto, Mariano I / Travaglini, Kyle J / Rachleff, Victoria M / Kaplan, Eitan S / Long, Brian / Ariza, Jeanelle / Ding, Yi / Mahoney, Joseph T / Dee, Nick / Goldy, Jeff / Melief, Erica J / Brouner, Krissy / Campos, John / Carr, Ambrose J / Casper, Tamara / Chakrabarty, Rushil / Clark, Michael / Compos, Jazmin / Cool, Jonah /
    Valera Cuevas, Nasmil J / Dalley, Rachel / Darvas, Martin / Ding, Song-Lin / Dolbeare, Tim / Mac Donald, Christine L / Egdorf, Tom / Esposito, Luke / Ferrer, Rebecca / Gala, Rohan / Gary, Amanda / Gloe, Jessica / Guilford, Nathan / Guzman, Junitta / Ho, Windy / Jarksy, Tim / Johansen, Nelson / Kalmbach, Brian E / Keene, Lisa M / Khawand, Sarah / Kilgore, Mitch / Kirkland, Amanda / Kunst, Michael / Lee, Brian R / Malone, Jocelin / Maltzer, Zoe / Martin, Naomi / McCue, Rachel / McMillen, Delissa / Meyerdierks, Emma / Meyers, Kelly P / Mollenkopf, Tyler / Montine, Mark / Nolan, Amber L / Nyhus, Julie / Olsen, Paul A / Pacleb, Maiya / Pham, Thanh / Pom, Christina Alice / Postupna, Nadia / Ruiz, Augustin / Schantz, Aimee M / Sorensen, Staci A / Staats, Brian / Sullivan, Matt / Sunkin, Susan M / Thompson, Carol / Tieu, Michael / Ting, Jonathan / Torkelson, Amy / Tran, Tracy / Wang, Ming-Qiang / Waters, Jack / Wilson, Angela M / Haynor, David / Gatto, Nicole / Jayadev, Suman / Mufti, Shoaib / Ng, Lydia / Mukherjee, Shubhabrata / Crane, Paul K / Latimer, Caitlin S / Levi, Boaz P / Smith, Kimberly / Close, Jennie L / Miller, Jeremy A / Hodge, Rebecca D / Larson, Eric B / Grabowski, Thomas J / Hawrylycz, Michael / Keene, C Dirk / Lein, Ed S

    Research square

    2023  

    Abstract: 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 cellular mechanisms ... ...

    Abstract 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 cellular mechanisms driving AD progression and vulnerable cell populations affected by disease remain coarsely understood. The current study harnesses single cell and spatial genomics tools and knowledge from the BRAIN Initiative Cell Census Network to understand the impact of disease progression on middle temporal gyrus cell types. We used image-based quantitative neuropathology to place 84 donors spanning the spectrum of AD pathology along a continuous disease pseudoprogression score and multiomic technologies to profile single nuclei from each donor, mapping their transcriptomes, epigenomes, and spatial coordinates to a common cell type reference with unprecedented resolution. Temporal analysis of cell-type proportions indicated an early reduction of Somatostatin-expressing neuronal subtypes and a late decrease of supragranular intratelencephalic-projecting excitatory and Parvalbumin-expressing neurons, with increases in disease-associated microglial and astrocytic states. We found complex gene expression differences, ranging from global to cell type-specific effects. These effects showed different temporal patterns indicating diverse cellular perturbations as a function of disease progression. A subset of donors showed a particularly severe cellular and molecular phenotype, which correlated with steeper cognitive decline. We have created a freely available public resource to explore these data and to accelerate progress in AD research at SEA-AD.org.
    Language English
    Publishing date 2023-05-23
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2921860/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Enhancer viruses for combinatorial cell-subclass-specific labeling.

    Graybuck, Lucas T / Daigle, Tanya L / Sedeño-Cortés, Adriana E / Walker, Miranda / Kalmbach, Brian / Lenz, Garreck H / Morin, Elyse / Nguyen, Thuc Nghi / Garren, Emma / Bendrick, Jacqueline L / Kim, Tae Kyung / Zhou, Thomas / Mortrud, Marty / Yao, Shenqin / Siverts, La' Akea / Larsen, Rachael / Gore, Bryan B / Szelenyi, Eric R / Trader, Cameron /
    Balaram, Pooja / van Velthoven, Cindy T J / Chiang, Megan / Mich, John K / Dee, Nick / Goldy, Jeff / Cetin, Ali H / Smith, Kimberly / Way, Sharon W / Esposito, Luke / Yao, Zizhen / Gradinaru, Viviana / Sunkin, Susan M / Lein, Ed / Levi, Boaz P / Ting, Jonathan T / Zeng, Hongkui / Tasic, Bosiljka

    Neuron

    2021  Volume 109, Issue 9, Page(s) 1449–1464.e13

    Abstract: Rapid cell type identification by new genomic single-cell analysis methods has not been met with efficient experimental access to these cell types. To facilitate access to specific neural populations in mouse cortex, we collected chromatin accessibility ... ...

    Abstract Rapid cell type identification by new genomic single-cell analysis methods has not been met with efficient experimental access to these cell types. To facilitate access to specific neural populations in mouse cortex, we collected chromatin accessibility data from individual cells and identified enhancers specific for cell subclasses and types. When cloned into recombinant adeno-associated viruses (AAVs) and delivered to the brain, these enhancers drive transgene expression in specific cortical cell subclasses. We extensively characterized several enhancer AAVs to show that they label different projection neuron subclasses as well as a homologous neuron subclass in human cortical slices. We also show how coupling enhancer viruses expressing recombinases to a newly generated transgenic mouse, Ai213, enables strong labeling of three different neuronal classes/subclasses in the brain of a single transgenic animal. This approach combines unprecedented flexibility with specificity for investigation of cell types in the mouse brain and beyond.
    MeSH term(s) Animals ; Brain/cytology ; Datasets as Topic ; Dependovirus ; Humans ; Mice ; Mice, Transgenic ; Neurons/classification ; Neurons/cytology ; Single-Cell Analysis/methods
    Language English
    Publishing date 2021-03-30
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2021.03.011
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  8. Article ; Online: Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex.

    Lee, Brian R / Dalley, Rachel / Miller, Jeremy A / Chartrand, Thomas / Close, Jennie / Mann, Rusty / Mukora, Alice / Ng, Lindsay / Alfiler, Lauren / Baker, Katherine / Bertagnolli, Darren / Brouner, Krissy / Casper, Tamara / Csajbok, Eva / Donadio, Nicholas / Driessens, Stan L W / Egdorf, Tom / Enstrom, Rachel / Galakhova, Anna A /
    Gary, Amanda / Gelfand, Emily / Goldy, Jeff / Hadley, Kristen / Heistek, Tim S / Hill, Dijon / Hou, Wen-Hsien / Johansen, Nelson / Jorstad, Nik / Kim, Lisa / Kocsis, Agnes Katalin / Kruse, Lauren / Kunst, Michael / León, Gabriela / Long, Brian / Mallory, Matthew / Maxwell, Michelle / McGraw, Medea / McMillen, Delissa / Melief, Erica J / Molnar, Gabor / Mortrud, Marty T / Newman, Dakota / Nyhus, Julie / Opitz-Araya, Ximena / Ozsvár, Attila / Pham, Trangthanh / Pom, Alice / Potekhina, Lydia / Rajanbabu, Ram / Ruiz, Augustin / Sunkin, Susan M / Szöts, Ildikó / Taskin, Naz / Thyagarajan, Bargavi / Tieu, Michael / Trinh, Jessica / Vargas, Sara / Vumbaco, David / Waleboer, Femke / Walling-Bell, Sarah / Weed, Natalie / Williams, Grace / Wilson, Julia / Yao, Shenqin / Zhou, Thomas / Barzó, Pál / Bakken, Trygve / Cobbs, Charles / Dee, Nick / Ellenbogen, Richard G / Esposito, Luke / Ferreira, Manuel / Gouwens, Nathan W / Grannan, Benjamin / Gwinn, Ryder P / Hauptman, Jason S / Hodge, Rebecca / Jarsky, Tim / Keene, C Dirk / Ko, Andrew L / Korshoej, Anders Rosendal / Levi, Boaz P / Meier, Kaare / Ojemann, Jeffrey G / Patel, Anoop / Ruzevick, Jacob / Silbergeld, Daniel L / Smith, Kimberly / Sørensen, Jens Christian / Waters, Jack / Zeng, Hongkui / Berg, Jim / Capogna, Marco / Goriounova, Natalia A / Kalmbach, Brian / de Kock, Christiaan P J / Mansvelder, Huib D / Sorensen, Staci A / Tamas, Gabor / Lein, Ed S / Ting, Jonathan T

    Science (New York, N.Y.)

    2023  Volume 382, Issue 6667, Page(s) eadf6484

    Abstract: 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 plus Patch-seq ( ... ...

    Abstract 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 plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.
    MeSH term(s) Animals ; Humans ; Mice ; Electrophysiological Phenomena ; GABAergic Neurons/metabolism ; gamma-Aminobutyric Acid/metabolism ; Interneurons/metabolism ; Neocortex/cytology ; Neocortex/metabolism ; Patch-Clamp Techniques
    Chemical Substances gamma-Aminobutyric Acid (56-12-2)
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adf6484
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

    Chartrand, Thomas / Dalley, Rachel / Close, Jennie / Goriounova, Natalia A / Lee, Brian R / Mann, Rusty / Miller, Jeremy A / Molnar, Gabor / Mukora, Alice / Alfiler, Lauren / Baker, Katherine / Bakken, Trygve E / Berg, Jim / Bertagnolli, Darren / Braun, Thomas / Brouner, Krissy / Casper, Tamara / Csajbok, Eva Adrienn / Dee, Nick /
    Egdorf, Tom / Enstrom, Rachel / Galakhova, Anna A / Gary, Amanda / Gelfand, Emily / Goldy, Jeff / Hadley, Kristen / Heistek, Tim S / Hill, DiJon / Jorstad, Nik / Kim, Lisa / Kocsis, Agnes Katalin / Kruse, Lauren / Kunst, Michael / Leon, Gabriela / Long, Brian / Mallory, Matthew / McGraw, Medea / McMillen, Delissa / Melief, Erica J / Mihut, Norbert / Ng, Lindsay / Nyhus, Julie / Oláh, Gáspár / Ozsvár, Attila / Omstead, Victoria / Peterfi, Zoltan / Pom, Alice / Potekhina, Lydia / Rajanbabu, Ramkumar / Rozsa, Marton / Ruiz, Augustin / Sandle, Joanna / Sunkin, Susan M / Szots, Ildiko / Tieu, Michael / Toth, Martin / Trinh, Jessica / Vargas, Sara / Vumbaco, David / Williams, Grace / Wilson, Julia / Yao, Zizhen / Barzo, Pal / Cobbs, Charles / Ellenbogen, Richard G / Esposito, Luke / Ferreira, Manuel / Gouwens, Nathan W / Grannan, Benjamin / Gwinn, Ryder P / Hauptman, Jason S / Jarsky, Tim / Keene, C Dirk / Ko, Andrew L / Koch, Christof / Ojemann, Jeffrey G / Patel, Anoop / Ruzevick, Jacob / Silbergeld, Daniel L / Smith, Kimberly / Sorensen, Staci A / Tasic, Bosiljka / Ting, Jonathan T / Waters, Jack / de Kock, Christiaan P J / Mansvelder, Huib D / Tamas, Gabor / Zeng, Hongkui / Kalmbach, Brian / Lein, Ed S

    Science (New York, N.Y.)

    2023  Volume 382, Issue 6667, Page(s) eadf0805

    Abstract: 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 distinctive ... ...

    Abstract 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 distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.
    MeSH term(s) Animals ; Humans ; Mice ; Axons/metabolism ; Interneurons/metabolism ; Neocortex/cytology ; Neocortex/metabolism ; Pyramidal Cells/metabolism ; Transcriptome
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adf0805
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  10. Article ; Online: A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain.

    Yao, Zizhen / van Velthoven, Cindy T J / Kunst, Michael / Zhang, Meng / McMillen, Delissa / Lee, Changkyu / Jung, Won / Goldy, Jeff / Abdelhak, Aliya / Aitken, Matthew / Baker, Katherine / Baker, Pamela / Barkan, Eliza / Bertagnolli, Darren / Bhandiwad, Ashwin / Bielstein, Cameron / Bishwakarma, Prajal / Campos, Jazmin / Carey, Daniel /
    Casper, Tamara / Chakka, Anish Bhaswanth / Chakrabarty, Rushil / Chavan, Sakshi / Chen, Min / Clark, Michael / Close, Jennie / Crichton, Kirsten / Daniel, Scott / DiValentin, Peter / Dolbeare, Tim / Ellingwood, Lauren / Fiabane, Elysha / Fliss, Timothy / Gee, James / Gerstenberger, James / Glandon, Alexandra / Gloe, Jessica / Gould, Joshua / Gray, James / Guilford, Nathan / Guzman, Junitta / Hirschstein, Daniel / Ho, Windy / Hooper, Marcus / Huang, Mike / Hupp, Madie / Jin, Kelly / Kroll, Matthew / Lathia, Kanan / Leon, Arielle / Li, Su / Long, Brian / Madigan, Zach / Malloy, Jessica / Malone, Jocelin / Maltzer, Zoe / Martin, Naomi / McCue, Rachel / McGinty, Ryan / Mei, Nicholas / Melchor, Jose / Meyerdierks, Emma / Mollenkopf, Tyler / Moonsman, Skyler / Nguyen, Thuc Nghi / Otto, Sven / Pham, Trangthanh / Rimorin, Christine / Ruiz, Augustin / Sanchez, Raymond / Sawyer, Lane / Shapovalova, Nadiya / Shepard, Noah / Slaughterbeck, Cliff / Sulc, Josef / Tieu, Michael / Torkelson, Amy / Tung, Herman / Valera Cuevas, Nasmil / Vance, Shane / Wadhwani, Katherine / Ward, Katelyn / Levi, Boaz / Farrell, Colin / Young, Rob / Staats, Brian / Wang, Ming-Qiang Michael / Thompson, Carol L / Mufti, Shoaib / Pagan, Chelsea M / Kruse, Lauren / Dee, Nick / Sunkin, Susan M / Esposito, Luke / Hawrylycz, Michael J / Waters, Jack / Ng, Lydia / Smith, Kimberly / Tasic, Bosiljka / Zhuang, Xiaowei / Zeng, Hongkui

    Nature

    2023  Volume 624, Issue 7991, Page(s) 317–332

    Abstract: 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 ... ...

    Abstract 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
    MeSH term(s) Animals ; Mice ; Brain/anatomy & histology ; Brain/cytology ; Brain/metabolism ; Datasets as Topic ; Gene Expression Profiling ; In Situ Hybridization, Fluorescence ; Neural Pathways ; Neurons/classification ; Neurons/metabolism ; Neuropeptides/metabolism ; Neurotransmitter Agents/metabolism ; RNA/analysis ; Single-Cell Gene Expression Analysis ; Transcription Factors/metabolism ; Transcriptome/genetics
    Chemical Substances Neuropeptides ; Neurotransmitter Agents ; RNA (63231-63-0) ; Transcription Factors
    Language English
    Publishing date 2023-12-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06812-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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