A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons

Among the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to...

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Main Authors: Benjamin W Okaty, Nikita Sturrock, Yasmin Escobedo Lozoya, YoonJeung Chang, Rebecca A Senft, Krissy A Lyon, Olga V Alekseyenko, Susan M Dymecki
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2020-06-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/55523
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author Benjamin W Okaty
Nikita Sturrock
Yasmin Escobedo Lozoya
YoonJeung Chang
Rebecca A Senft
Krissy A Lyon
Olga V Alekseyenko
Susan M Dymecki
author_facet Benjamin W Okaty
Nikita Sturrock
Yasmin Escobedo Lozoya
YoonJeung Chang
Rebecca A Senft
Krissy A Lyon
Olga V Alekseyenko
Susan M Dymecki
author_sort Benjamin W Okaty
collection DOAJ
description Among the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to treat affective disorders. Characterizing Pet1 neuron molecular heterogeneity and relating it to anatomy is vital for understanding DR functional organization, with potential to inform therapeutic separability. Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-Pet1 neurons. We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR. We further show that P2ry1-Pet1 DR neurons – the most molecularly distinct subtype – possess unique efferent projections and electrophysiological properties. These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomic identification of Pet1 neuron subtypes.
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spelling doaj.art-500b85e0a61c417fad43b75c40ff11322022-12-22T02:01:23ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.55523A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neuronsBenjamin W Okaty0https://orcid.org/0000-0003-1281-2244Nikita Sturrock1https://orcid.org/0000-0002-1635-6760Yasmin Escobedo Lozoya2https://orcid.org/0000-0001-8197-770XYoonJeung Chang3https://orcid.org/0000-0001-9549-8208Rebecca A Senft4https://orcid.org/0000-0003-0081-4170Krissy A Lyon5https://orcid.org/0000-0002-4453-8406Olga V Alekseyenko6https://orcid.org/0000-0003-1645-5133Susan M Dymecki7https://orcid.org/0000-0003-0910-9881Department of Genetics, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesDepartment of Genetics, Harvard Medical School, Boston, United StatesAmong the brainstem raphe nuclei, the dorsal raphe nucleus (DR) contains the greatest number of Pet1-lineage neurons, a predominantly serotonergic group distributed throughout DR subdomains. These neurons collectively regulate diverse physiology and behavior and are often therapeutically targeted to treat affective disorders. Characterizing Pet1 neuron molecular heterogeneity and relating it to anatomy is vital for understanding DR functional organization, with potential to inform therapeutic separability. Here we use high-throughput and DR subdomain-targeted single-cell transcriptomics and intersectional genetic tools to map molecular and anatomical diversity of DR-Pet1 neurons. We describe up to fourteen neuron subtypes, many showing biased cell body distributions across the DR. We further show that P2ry1-Pet1 DR neurons – the most molecularly distinct subtype – possess unique efferent projections and electrophysiological properties. These data complement and extend previous DR characterizations, combining intersectional genetics with multiple transcriptomic modalities to achieve fine-scale molecular and anatomic identification of Pet1 neuron subtypes.https://elifesciences.org/articles/55523serotonindorsal raphePet1single cell RNA-seqserotonin neuronsneuronal diversity
spellingShingle Benjamin W Okaty
Nikita Sturrock
Yasmin Escobedo Lozoya
YoonJeung Chang
Rebecca A Senft
Krissy A Lyon
Olga V Alekseyenko
Susan M Dymecki
A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons
eLife
serotonin
dorsal raphe
Pet1
single cell RNA-seq
serotonin neurons
neuronal diversity
title A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons
title_full A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons
title_fullStr A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons
title_full_unstemmed A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons
title_short A single-cell transcriptomic and anatomic atlas of mouse dorsal raphe Pet1 neurons
title_sort single cell transcriptomic and anatomic atlas of mouse dorsal raphe pet1 neurons
topic serotonin
dorsal raphe
Pet1
single cell RNA-seq
serotonin neurons
neuronal diversity
url https://elifesciences.org/articles/55523
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