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A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution

Author

Listed:
  • Stefano Nardone

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Roberto Luca

    (Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Antonino Zito

    (King’s College London
    Massachusetts General Hospital
    The Blavatnik Institute, Harvard Medical School)

  • Nataliya Klymko

    (Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave)

  • Dimitris Nicoloutsopoulos

    (University College London)

  • Oren Amsalem

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Cory Brannigan

    (HEAVY.AI, 100 Montgomery St Fl 5, San Francisco)

  • Jon M. Resch

    (University of Iowa
    Fraternal Order of Eagles Diabetes Research Center. University of Iowa Carver College of Medicine)

  • Christopher L. Jacobs

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Deepti Pant

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Molly Veregge

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Harini Srinivasan

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Ryan M. Grippo

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Zongfang Yang

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Mark L. Zeidel

    (Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave)

  • Mark L. Andermann

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Kenneth D. Harris

    (University College London)

  • Linus T. Tsai

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Elda Arrigoni

    (Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Anne M. J. Verstegen

    (Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave)

  • Clifford B. Saper

    (Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School)

  • Bradford B. Lowell

    (Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School)

Abstract

The “dorsal pons”, or “dorsal pontine tegmentum” (dPnTg), is part of the brainstem. It is a complex, densely packed region whose nuclei are involved in regulating many vital functions. Notable among them are the parabrachial nucleus, the Kölliker Fuse, the Barrington nucleus, the locus coeruleus, and the dorsal, laterodorsal, and ventral tegmental nuclei. In this study, we applied single-nucleus RNA-seq (snRNA-seq) to resolve neuronal subtypes based on their unique transcriptional profiles and then used multiplexed error robust fluorescence in situ hybridization (MERFISH) to map them spatially. We sampled ~1 million cells across the dPnTg and defined the spatial distribution of over 120 neuronal subtypes. Our analysis identified an unpredicted high transcriptional diversity in this region and pinpointed the unique marker genes of many neuronal subtypes. We also demonstrated that many neuronal subtypes are transcriptionally similar between humans and mice, enhancing this study’s translational value. Finally, we developed a freely accessible, GPU and CPU-powered dashboard ( http://harvard.heavy.ai:6273/ ) that combines interactive visual analytics and hardware-accelerated SQL into a data science framework to allow the scientific community to query and gain insights into the data.

Suggested Citation

  • Stefano Nardone & Roberto Luca & Antonino Zito & Nataliya Klymko & Dimitris Nicoloutsopoulos & Oren Amsalem & Cory Brannigan & Jon M. Resch & Christopher L. Jacobs & Deepti Pant & Molly Veregge & Hari, 2024. "A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45907-7
    DOI: 10.1038/s41467-024-45907-7
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    References listed on IDEAS

    as
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