Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling.
Identifieur interne : 000640 ( PubMed/Curation ); précédent : 000639; suivant : 000641Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling.
Auteurs : Jean-Francois Poulin [États-Unis] ; Jian Zou [États-Unis] ; Janelle Drouin-Ouellet [Royaume-Uni] ; Kwang-Youn A. Kim [États-Unis] ; Francesca Cicchetti [Canada] ; Rajeshwar B. Awatramani [États-Unis]Source :
- Cell reports [ 2211-1247 ] ; 2014.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Aging (metabolism), Animals, Disease Models, Animal, Dopaminergic Neurons (classification), Dopaminergic Neurons (cytology), Dopaminergic Neurons (metabolism), Gene Expression Profiling, High-Throughput Screening Assays, Mesencephalon (cytology), Mice, Inbred C57BL, Parkinson Disease (pathology).
- MESH :
- chemical : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- classification : Dopaminergic Neurons.
- cytology : Dopaminergic Neurons, Mesencephalon.
- metabolism : Aging, Dopaminergic Neurons.
- pathology : Parkinson Disease.
- Animals, Disease Models, Animal, Gene Expression Profiling, High-Throughput Screening Assays, Mice, Inbred C57BL.
Abstract
Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we successfully identified multiple molecularly distinct dopamine neuron subtypes and localized them in the adult mouse brain. To validate the anatomical and functional correlates of molecular diversity, we provide evidence that one Vip+ subtype, located in the periaqueductal region, has a discrete projection field within the extended amygdala. Another Aldh1a1+ subtype, located in the substantia nigra, is especially vulnerable in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Overall, this rapid, cost-effective approach enables the identification and classification of multiple dopamine neuron subtypes, with distinct molecular, anatomical, and functional properties.
DOI: 10.1016/j.celrep.2014.10.008
PubMed: 25437550
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Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we successfully identified multiple molecularly distinct dopamine neuron subtypes and localized them in the adult mouse brain. To validate the anatomical and functional correlates of molecular diversity, we provide evidence that one Vip+ subtype, located in the periaqueductal region, has a discrete projection field within the extended amygdala. Another Aldh1a1+ subtype, located in the substantia nigra, is especially vulnerable in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Overall, this rapid, cost-effective approach enables the identification and classification of multiple dopamine neuron subtypes, with distinct molecular, anatomical, and functional properties.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25437550</PMID><DateCreated><Year>2014</Year><Month>12</Month><Day>02</Day></DateCreated><DateCompleted><Year>2015</Year><Month>07</Month><Day>23</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2211-1247</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>3</Issue><PubDate><Year>2014</Year><Month>Nov</Month><Day>06</Day></PubDate></JournalIssue><Title>Cell reports</Title><ISOAbbreviation>Cell Rep</ISOAbbreviation></Journal><ArticleTitle>Defining midbrain dopaminergic neuron diversity by single-cell gene expression profiling.</ArticleTitle><Pagination><MedlinePgn>930-43</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.celrep.2014.10.008</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S2211-1247(14)00862-6</ELocationID><Abstract><AbstractText>Effective approaches to neuropsychiatric disorders require detailed understanding of the cellular composition and circuitry of the complex mammalian brain. Here, we present a paradigm for deconstructing the diversity of neurons defined by a specific neurotransmitter using a microfluidic dynamic array to simultaneously evaluate the expression of 96 genes in single neurons. With this approach, we successfully identified multiple molecularly distinct dopamine neuron subtypes and localized them in the adult mouse brain. To validate the anatomical and functional correlates of molecular diversity, we provide evidence that one Vip+ subtype, located in the periaqueductal region, has a discrete projection field within the extended amygdala. Another Aldh1a1+ subtype, located in the substantia nigra, is especially vulnerable in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Overall, this rapid, cost-effective approach enables the identification and classification of multiple dopamine neuron subtypes, with distinct molecular, anatomical, and functional properties.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Poulin</LastName><ForeName>Jean-Francois</ForeName><Initials>JF</Initials><AffiliationInfo><Affiliation>Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zou</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Drouin-Ouellet</LastName><ForeName>Janelle</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>John van Geest Centre for Brain Repair, University of Cambridge, Cambridge CB2 0PY, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Kwang-Youn A</ForeName><Initials>KY</Initials><AffiliationInfo><Affiliation>Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cicchetti</LastName><ForeName>Francesca</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Centre de Recherche du CHU de Québec, Axe Neurosciences and Université Laval, Québec, QC G1V 4G2, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Awatramani</LastName><ForeName>Rajeshwar B</ForeName><Initials>RB</Initials><AffiliationInfo><Affiliation>Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: r-awatramani@northwestern.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>UL1 TR000150</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1RR025741</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 NS072703</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 RR025741</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA060553</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>1R21NS072703-01</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>10</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell Rep</MedlineTA><NlmUniqueID>101573691</NlmUniqueID></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>9P21XSP91P</RegistryNumber><NameOfSubstance UI="D015632">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Nature. 2010 Dec 2;468(7324):696-700</RefSource><PMID Version="1">21068725</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2011 Mar 17;471(7338):358-62</RefSource><PMID 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