IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31336-x.html
   My bibliography  Save this article

Cyclic microchip assay for measurement of hundreds of functional proteins in single neurons

Author

Listed:
  • Liwei Yang

    (Stony Brook University)

  • Avery Ball

    (Stony Brook University)

  • Jesse Liu

    (Stony Brook University)

  • Tanya Jain

    (Memorial Sloan Kettering Cancer Center
    Weill Graduate School of Medical Sciences of Cornell University)

  • Yue-Ming Li

    (Memorial Sloan Kettering Cancer Center
    Weill Graduate School of Medical Sciences of Cornell University
    Weill Graduate School of Medical Sciences of Cornell University)

  • Firoz Akhter

    (Stony Brook University)

  • Donghui Zhu

    (Stony Brook University)

  • Jun Wang

    (Stony Brook University)

Abstract

Despite the fact that proteins carry out nearly all cellular functions and mark the differences of cells, the existing single-cell tools can only analyze dozens of proteins, a scale far from full characterization of cells and tissue yet. Herein, we present a single-cell cyclic multiplex in situ tagging (CycMIST) technology that affords the comprehensive functional proteome profiling of single cells. We demonstrate the technology by detecting 182 proteins that include surface markers, neuron function proteins, neurodegeneration markers, signaling pathway proteins, and transcription factors. Further studies on cells derived from the 5XFAD mice, an Alzheimer’s Disease (AD) model, validate the utility of our technology and reveal the deep heterogeneity of brain cells. Through comparison with control mouse cells, we have identified differentially expressed proteins in AD pathology. Our technology could offer new insights into cell machinery and thus may advance many fields including drug discovery, molecular diagnostics, and clinical studies.

Suggested Citation

  • Liwei Yang & Avery Ball & Jesse Liu & Tanya Jain & Yue-Ming Li & Firoz Akhter & Donghui Zhu & Jun Wang, 2022. "Cyclic microchip assay for measurement of hundreds of functional proteins in single neurons," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31336-x
    DOI: 10.1038/s41467-022-31336-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31336-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31336-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Hansruedi Mathys & Jose Davila-Velderrain & Zhuyu Peng & Fan Gao & Shahin Mohammadi & Jennie Z. Young & Madhvi Menon & Liang He & Fatema Abdurrob & Xueqiao Jiang & Anthony J. Martorell & Richard M. Ra, 2019. "Author Correction: Single-cell transcriptomic analysis of Alzheimer’s disease," Nature, Nature, vol. 571(7763), pages 1-1, July.
    2. Pavel Zrazhevskiy & Xiaohu Gao, 2013. "Quantum dot imaging platform for single-cell molecular profiling," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    3. Randy J. Giedt & Divya Pathania & Jonathan C. T. Carlson & Philip J. McFarland & Andres Fernandez Castillo & Dejan Juric & Ralph Weissleder, 2018. "Single-cell barcode analysis provides a rapid readout of cellular signaling pathways in clinical specimens," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    4. Hansruedi Mathys & Jose Davila-Velderrain & Zhuyu Peng & Fan Gao & Shahin Mohammadi & Jennie Z. Young & Madhvi Menon & Liang He & Fatema Abdurrob & Xueqiao Jiang & Anthony J. Martorell & Richard M. Ra, 2019. "Single-cell transcriptomic analysis of Alzheimer’s disease," Nature, Nature, vol. 570(7761), pages 332-337, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Özkan İş & Xue Wang & Joseph S. Reddy & Yuhao Min & Elanur Yilmaz & Prabesh Bhattarai & Tulsi Patel & Jeremiah Bergman & Zachary Quicksall & Michael G. Heckman & Frederick Q. Tutor-New & Birsen Can De, 2024. "Gliovascular transcriptional perturbations in Alzheimer’s disease reveal molecular mechanisms of blood brain barrier dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Nelson Johansen & Hongru Hu & Gerald Quon, 2023. "Projecting RNA measurements onto single cell atlases to extract cell type-specific expression profiles using scProjection," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Hannah Drew Rickner & Lulu Jiang & Rui Hong & Nicholas K. O’Neill & Chromewell A. Mojica & Benjamin J. Snyder & Lushuang Zhang & Dipan Shaw & Maria Medalla & Benjamin Wolozin & Christine S. Cheng, 2022. "Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    4. Jingtao Wang & Gregory J. Fonseca & Jun Ding, 2024. "scSemiProfiler: Advancing large-scale single-cell studies through semi-profiling with deep generative models and active learning," Nature Communications, Nature, vol. 15(1), pages 1-27, December.
    5. Hyun-Sik Yang & Ling Teng & Daniel Kang & Vilas Menon & Tian Ge & Hilary K. Finucane & Aaron P. Schultz & Michael Properzi & Hans-Ulrich Klein & Lori B. Chibnik & Julie A. Schneider & David A. Bennett, 2023. "Cell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Zoeb Jiwaji & Sachin S. Tiwari & Rolando X. Avilés-Reyes & Monique Hooley & David Hampton & Megan Torvell & Delinda A. Johnson & Jamie McQueen & Paul Baxter & Kayalvizhi Sabari-Sankar & Jing Qiu & Xin, 2022. "Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    7. Zu-Qiang Liu & Hao Dai & Lu Yao & Wei-Feng Chen & Yun Wang & Li-Yun Ma & Xiao-Qing Li & Sheng-Li Lin & Meng-Jiang He & Ping-Ting Gao & Xin-Yang Liu & Jia-Xin Xu & Xiao-Yue Xu & Ke-Hao Wang & Li Wang &, 2023. "A single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Chang Su & Zichun Xu & Xinning Shan & Biao Cai & Hongyu Zhao & Jingfei Zhang, 2023. "Cell-type-specific co-expression inference from single cell RNA-sequencing data," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. Jia-Ru Wei & Zhao-Zhe Hao & Chuan Xu & Mengyao Huang & Lei Tang & Nana Xu & Ruifeng Liu & Yuhui Shen & Sarah A. Teichmann & Zhichao Miao & Sheng Liu, 2022. "Identification of visual cortex cell types and species differences using single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    10. Nicola A. Kearns & Artemis Iatrou & Daniel J. Flood & Sashini Tissera & Zachary M. Mullaney & Jishu Xu & Chris Gaiteri & David A. Bennett & Yanling Wang, 2023. "Dissecting the human leptomeninges at single-cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. BaDoi N. Phan & Madelyn H. Ray & Xiangning Xue & Chen Fu & Robert J. Fenster & Stephen J. Kohut & Jack Bergman & Suzanne N. Haber & Kenneth M. McCullough & Madeline K. Fish & Jill R. Glausier & Qiao S, 2024. "Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. Cankun Wang & Diana Acosta & Megan McNutt & Jiang Bian & Anjun Ma & Hongjun Fu & Qin Ma, 2024. "A single-cell and spatial RNA-seq database for Alzheimer’s disease (ssREAD)," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    13. Osama Al-Dalahmah & Michael G. Argenziano & Adithya Kannan & Aayushi Mahajan & Julia Furnari & Fahad Paryani & Deborah Boyett & Akshay Save & Nelson Humala & Fatima Khan & Juncheng Li & Hong Lu & Yu S, 2023. "Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    14. Malosree Maitra & Haruka Mitsuhashi & Reza Rahimian & Anjali Chawla & Jennie Yang & Laura M. Fiori & Maria Antonietta Davoli & Kelly Perlman & Zahia Aouabed & Deborah C. Mash & Matthew Suderman & Nagu, 2023. "Cell type specific transcriptomic differences in depression show similar patterns between males and females but implicate distinct cell types and genes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Juan F. Quintana & Praveena Chandrasegaran & Matthew C. Sinton & Emma M. Briggs & Thomas D. Otto & Rhiannon Heslop & Calum Bentley-Abbot & Colin Loney & Luis de Lecea & Neil A. Mabbott & Annette MacLe, 2022. "Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    16. Shinya Tasaki & Jishu Xu & Denis R. Avey & Lynnaun Johnson & Vladislav A. Petyuk & Robert J. Dawe & David A. Bennett & Yanling Wang & Chris Gaiteri, 2022. "Inferring protein expression changes from mRNA in Alzheimer’s dementia using deep neural networks," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    17. Elaine T. Lim & Yingleong Chan & Pepper Dawes & Xiaoge Guo & Serkan Erdin & Derek J. C. Tai & Songlei Liu & Julia M. Reichert & Mannix J. Burns & Ying Kai Chan & Jessica J. Chiang & Katharina Meyer & , 2022. "Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    18. Anna Podleśny-Drabiniok & Gloriia Novikova & Yiyuan Liu & Josefine Dunst & Rose Temizer & Chiara Giannarelli & Samuele Marro & Taras Kreslavsky & Edoardo Marcora & Alison Mary Goate, 2024. "BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer’s disease and other disorders of lipid-rich tissues," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    19. Logan Brase & Shih-Feng You & Ricardo D’Oliveira Albanus & Jorge L. Del-Aguila & Yaoyi Dai & Brenna C. Novotny & Carolina Soriano-Tarraga & Taitea Dykstra & Maria Victoria Fernandez & John P. Budde & , 2023. "Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    20. Torben Johann Hausrat & Philipp C. Janiesch & Petra Breiden & David Lutz & Sabine Hoffmeister-Ullerich & Irm Hermans-Borgmeyer & Antonio Virgilio Failla & Matthias Kneussel, 2022. "Disruption of tubulin-alpha4a polyglutamylation prevents aggregation of hyper-phosphorylated tau and microglia activation in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31336-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.