Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei
Serotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a co...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/49424 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jing Ren Alina Isakova Drew Friedmann Jiawei Zeng Sophie M Grutzner Albert Pun Grace Q Zhao Sai Saroja Kolluru Ruiyu Wang Rui Lin Pengcheng Li Anan Li Jennifer L Raymond Qingming Luo Minmin Luo Stephen R Quake Liqun Luo |
| spellingShingle |
Jing Ren Alina Isakova Drew Friedmann Jiawei Zeng Sophie M Grutzner Albert Pun Grace Q Zhao Sai Saroja Kolluru Ruiyu Wang Rui Lin Pengcheng Li Anan Li Jennifer L Raymond Qingming Luo Minmin Luo Stephen R Quake Liqun Luo Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei eLife serotonin sc-RNAseq dorsal raphe medial raphe intersectional labeling single cell reconstruction |
| author_facet |
Jing Ren Alina Isakova Drew Friedmann Jiawei Zeng Sophie M Grutzner Albert Pun Grace Q Zhao Sai Saroja Kolluru Ruiyu Wang Rui Lin Pengcheng Li Anan Li Jennifer L Raymond Qingming Luo Minmin Luo Stephen R Quake Liqun Luo |
| author_sort |
Jing Ren |
| title |
Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei |
| title_short |
Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei |
| title_full |
Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei |
| title_fullStr |
Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei |
| title_full_unstemmed |
Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei |
| title_sort |
single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei |
| publisher |
eLife Sciences Publications Ltd |
| series |
eLife |
| issn |
2050-084X |
| publishDate |
2019-10-01 |
| description |
Serotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed diverse and segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes. |
| topic |
serotonin sc-RNAseq dorsal raphe medial raphe intersectional labeling single cell reconstruction |
| url |
https://elifesciences.org/articles/49424 |
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doaj-eb730726e1314fd5a7371c54603afbe42021-05-05T18:02:13ZengeLife Sciences Publications LtdeLife2050-084X2019-10-01810.7554/eLife.49424Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nucleiJing Ren0https://orcid.org/0000-0002-6665-7457Alina Isakova1https://orcid.org/0000-0003-1113-6889Drew Friedmann2Jiawei Zeng3Sophie M Grutzner4Albert Pun5Grace Q Zhao6Sai Saroja Kolluru7Ruiyu Wang8Rui Lin9Pengcheng Li10Anan Li11Jennifer L Raymond12https://orcid.org/0000-0002-8145-747XQingming Luo13https://orcid.org/0000-0002-6725-9311Minmin Luo14https://orcid.org/0000-0003-3535-6624Stephen R Quake15https://orcid.org/0000-0002-1613-0809Liqun Luo16https://orcid.org/0000-0001-5467-9264Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, United StatesDepartment of Bioengineering, Stanford University, Stanford, United States; Department of Applied Physics, Stanford University, Stanford, United StatesDepartment of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, United StatesNational Institute of Biological Science, Beijing, ChinaDepartment of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, United StatesDepartment of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, United StatesDepartment of Neurobiology, Stanford University School of Medicine, Stanford, United StatesDepartment of Bioengineering, Stanford University, Stanford, United States; Department of Applied Physics, Stanford University, Stanford, United StatesNational Institute of Biological Science, Beijing, ChinaNational Institute of Biological Science, Beijing, ChinaBritton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China; HUST-Suzhou Institute for Brainsmatics, JITRI Institute for Brainsmatics, Suzhou, ChinaBritton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China; HUST-Suzhou Institute for Brainsmatics, JITRI Institute for Brainsmatics, Suzhou, ChinaDepartment of Neurobiology, Stanford University School of Medicine, Stanford, United StatesBritton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, ChinaNational Institute of Biological Science, Beijing, China; School of Life Science, Tsinghua University, Beijing, ChinaDepartment of Bioengineering, Stanford University, Stanford, United States; Department of Applied Physics, Stanford University, Stanford, United States; Chan Zuckerberg Biohub, San Francisco, United StatesDepartment of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, United StatesSerotonin neurons of the dorsal and median raphe nuclei (DR, MR) collectively innervate the entire forebrain and midbrain, modulating diverse physiology and behavior. To gain a fundamental understanding of their molecular heterogeneity, we used plate-based single-cell RNA-sequencing to generate a comprehensive dataset comprising eleven transcriptomically distinct serotonin neuron clusters. Systematic in situ hybridization mapped specific clusters to the principal DR, caudal DR, or MR. These transcriptomic clusters differentially express a rich repertoire of neuropeptides, receptors, ion channels, and transcription factors. We generated novel intersectional viral-genetic tools to access specific subpopulations. Whole-brain axonal projection mapping revealed that DR serotonin neurons co-expressing vesicular glutamate transporter-3 preferentially innervate the cortex, whereas those co-expressing thyrotropin-releasing hormone innervate subcortical regions in particular the hypothalamus. Reconstruction of 50 individual DR serotonin neurons revealed diverse and segregated axonal projection patterns at the single-cell level. Together, these results provide a molecular foundation of the heterogenous serotonin neuronal phenotypes.https://elifesciences.org/articles/49424serotoninsc-RNAseqdorsal raphemedial rapheintersectional labelingsingle cell reconstruction |