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

Stefano Nardone; Roberto De Luca; Antonino Zito; Nataliya Klymko; Dimitris Nicoloutsopoulos; Oren Amsalem; Cory Brannigan; Jon M Resch; Christopher L Jacobs; Deepti Pant; Molly Veregge; Harini Srinivasan; Ryan M Grippo; Zongfang Yang; Mark L Zeidel; Mark L Andermann; Kenneth D Harris; Linus T Tsai; Elda Arrigoni; Anne M J Verstegen; Clifford B Saper; Bradford B Lowell

doi:10.1101/2023.09.18.558047

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

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

Stefano Nardone, Roberto De Luca, Antonino Zito, Nataliya Klymko, Dimitris Nicoloutsopoulos, Oren Amsalem, Cory Brannigan, Jon M Resch, Christopher L Jacobs, Deepti Pant, …

bioRxiv : the preprint server for biology

11/17/2023

DOI: 10.1101/2023.09.18.558047

PMCID: PMC10680649

PMID: 38014113

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Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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 many neuronal subtypes' unique marker genes. 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.

Details

Title: Subtitle: A spatially-resolved transcriptional atlas of the murine dorsal pons at single-cell resolution
Creators: Stefano Nardone - Broad Institute
Roberto De Luca - Beth Israel Deaconess Medical Center
Antonino Zito - King's College London
Nataliya Klymko - Beth Israel Deaconess Medical Center
Dimitris Nicoloutsopoulos - UCL Queen Square Institute of Neurology, University College London, London, UK
Oren Amsalem - Beth Israel Deaconess Medical Center
Cory Brannigan - HEAVY.AI, 100 Montgomery St Fl 5, San Francisco, California, 94104, USA
Jon M Resch - University of Iowa
Christopher L Jacobs - Broad Institute
Deepti Pant - Beth Israel Deaconess Medical Center
Molly Veregge - Beth Israel Deaconess Medical Center
Harini Srinivasan - Broad Institute
Ryan M Grippo - Beth Israel Deaconess Medical Center
Zongfang Yang - Beth Israel Deaconess Medical Center
Mark L Zeidel - Beth Israel Deaconess Medical Center
Mark L Andermann - Beth Israel Deaconess Medical Center
Kenneth D Harris - UCL Queen Square Institute of Neurology, University College London, London, UK
Linus T Tsai - Broad Institute
Elda Arrigoni - Beth Israel Deaconess Medical Center
Anne M J Verstegen - Beth Israel Deaconess Medical Center
Clifford B Saper - Beth Israel Deaconess Medical Center
Bradford B Lowell - Beth Israel Deaconess Medical Center
Resource Type: Preprint
Publication Details: bioRxiv : the preprint server for biology
DOI: 10.1101/2023.09.18.558047
PMID: 38014113
PMCID: PMC10680649
Publisher: United States
Grant note: DP1 AT010971 / NCCIH NIH HHS P01 HL149630 / NHLBI NIH HHS R01 DK075632 / NIDDK NIH HHS R01 DK113030 / NIDDK NIH HHS R01 NS091126 / NINDS NIH HHS R01 DK125708 / NIDDK NIH HHS R00 HL144923 / NHLBI NIH HHS P20 DK119789 / NIDDK NIH HHS R01 NS072337 / NINDS NIH HHS F32 MH012343 / NIMH NIH HHS
Language: English
Date posted: 11/17/2023
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984528128602771

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