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

Autor: Nardone S; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., De Luca R; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Zito A; Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.; Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA, USA., Klymko N; Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA., Nicoloutsopoulos D; UCL Queen Square Institute of Neurology, University College London, London, UK., Amsalem O; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Brannigan C; HEAVY.AI, 100 Montgomery St Fl 5, San Francisco, California, 94104, USA., Resch JM; Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, IA, USA.; Fraternal Order of Eagles Diabetes Research Center. University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA., Jacobs CL; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Pant D; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Veregge M; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Srinivasan H; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Grippo RM; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Yang Z; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Zeidel ML; Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA., Andermann ML; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA., Harris KD; UCL Queen Square Institute of Neurology, University College London, London, UK., Tsai LT; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Arrigoni E; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA., Verstegen AMJ; Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA, 02215, USA. aversteg@bidmc.harvard.edu., Saper CB; Department of Neurology, Division of Sleep Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA. csaper@bidmc.harvard.edu., Lowell BB; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. blowell@bidmc.harvard.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Mar 04; Vol. 15 (1), pp. 1966. Date of Electronic Publication: 2024 Mar 04.
DOI: 10.1038/s41467-024-45907-7
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE