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  1. Artikel: 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.
    Sprache Englisch
    Erscheinungsdatum 2023-03-06
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.03.06.531121
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: 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.
    Sprache Englisch
    Erscheinungsdatum 2023-05-23
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.21203/rs.3.rs-2921860/v1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; 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  Band 624, Heft 7991, Seite(n) 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-Begriff(e) 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
    Chemische Substanzen Neuropeptides ; Neurotransmitter Agents ; RNA (63231-63-0) ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2023-12-13
    Erscheinungsland England
    Dokumenttyp 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
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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