Defining midbrain dopaminergic neuron diversity by single-cell gene profiling
Identifieur interne : 000767 ( Pmc/Corpus ); précédent : 000766; suivant : 000768Defining midbrain dopaminergic neuron diversity by single-cell gene profiling
Auteurs : Jean-Francois Poulin ; Jian Zou ; Janelle Drouin-Ouellet ; Kwang-Youn A. Kim ; Francesca Cicchetti ; Rajeshwar B. AwatramaniSource :
- Cell reports [ 2211-1247 ] ; 2014.
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 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.
Url:
DOI: 10.1016/j.celrep.2014.10.008
PubMed: 25437550
PubMed Central: 4251558
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PMC:4251558Le document en format XML
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Kim</name><affiliation><nlm:aff id="A3">Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, 60611</nlm:aff></affiliation></author><author><name sortKey="Cicchetti, Francesca" sort="Cicchetti, Francesca" uniqKey="Cicchetti F" first="Francesca" last="Cicchetti">Francesca Cicchetti</name><affiliation><nlm:aff id="A4">Centre de recherche du CHU de Québec, Axe Neurosciences and Université Laval, Québec, QC, Canada, G1V 4G2</nlm:aff></affiliation></author><author><name sortKey="Awatramani, Rajeshwar B" sort="Awatramani, Rajeshwar B" uniqKey="Awatramani R" first="Rajeshwar B" last="Awatramani">Rajeshwar B. Awatramani</name><affiliation><nlm:aff id="A1">Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL, USA, 60611</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25437550</idno><idno type="pmc">4251558</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251558</idno><idno type="RBID">PMC:4251558</idno><idno type="doi">10.1016/j.celrep.2014.10.008</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000767</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000767</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Defining midbrain dopaminergic neuron diversity by single-cell gene profiling</title><author><name sortKey="Poulin, Jean Francois" sort="Poulin, Jean Francois" uniqKey="Poulin J" first="Jean-Francois" last="Poulin">Jean-Francois Poulin</name><affiliation><nlm:aff id="A1">Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL, USA, 60611</nlm:aff></affiliation></author><author><name sortKey="Zou, Jian" sort="Zou, Jian" uniqKey="Zou J" first="Jian" last="Zou">Jian Zou</name><affiliation><nlm:aff id="A1">Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL, USA, 60611</nlm:aff></affiliation></author><author><name sortKey="Drouin Ouellet, Janelle" sort="Drouin Ouellet, Janelle" uniqKey="Drouin Ouellet J" first="Janelle" last="Drouin-Ouellet">Janelle Drouin-Ouellet</name><affiliation><nlm:aff id="A2">John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom, CB2 0PY</nlm:aff></affiliation></author><author><name sortKey="Kim, Kwang Youn A" sort="Kim, Kwang Youn A" uniqKey="Kim K" first="Kwang-Youn A" last="Kim">Kwang-Youn A. Kim</name><affiliation><nlm:aff id="A3">Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, 60611</nlm:aff></affiliation></author><author><name sortKey="Cicchetti, Francesca" sort="Cicchetti, Francesca" uniqKey="Cicchetti F" first="Francesca" last="Cicchetti">Francesca Cicchetti</name><affiliation><nlm:aff id="A4">Centre de recherche du CHU de Québec, Axe Neurosciences and Université Laval, Québec, QC, Canada, G1V 4G2</nlm:aff></affiliation></author><author><name sortKey="Awatramani, Rajeshwar B" sort="Awatramani, Rajeshwar B" uniqKey="Awatramani R" first="Rajeshwar B" last="Awatramani">Rajeshwar B. Awatramani</name><affiliation><nlm:aff id="A1">Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL, USA, 60611</nlm:aff></affiliation></author></analytic><series><title level="j">Cell reports</title><idno type="eISSN">2211-1247</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">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 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.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101573691</journal-id><journal-id journal-id-type="pubmed-jr-id">39703</journal-id><journal-id journal-id-type="nlm-ta">Cell Rep</journal-id><journal-id journal-id-type="iso-abbrev">Cell Rep</journal-id><journal-title-group><journal-title>Cell reports</journal-title></journal-title-group><issn pub-type="epub">2211-1247</issn></journal-meta><article-meta><article-id pub-id-type="pmid">25437550</article-id><article-id pub-id-type="pmc">4251558</article-id><article-id pub-id-type="doi">10.1016/j.celrep.2014.10.008</article-id><article-id pub-id-type="manuscript">NIHMS634158</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Defining midbrain dopaminergic neuron diversity by single-cell gene profiling</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Poulin</surname><given-names>Jean-Francois</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Zou</surname><given-names>Jian</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Drouin-Ouellet</surname><given-names>Janelle</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Kwang-Youn A</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Cicchetti</surname><given-names>Francesca</given-names></name><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Awatramani</surname><given-names>Rajeshwar B</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Neurology and the Center for Genetic Medicine, Northwestern University, Chicago, IL, USA, 60611</aff><aff id="A2"><label>2</label>John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom, CB2 0PY</aff><aff id="A3"><label>3</label>Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, 60611</aff><aff id="A4"><label>4</label>Centre de recherche du CHU de Québec, Axe Neurosciences and Université Laval, Québec, QC, Canada, G1V 4G2</aff><author-notes><corresp id="cor1"><label>*</label>Corresponding author: <email>r-awatramani@northwestern.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>9</day><month>10</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>30</day><month>10</month><year>2014</year></pub-date><pub-date pub-type="ppub"><day>6</day><month>11</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>06</day><month>11</month><year>2015</year></pub-date><volume>9</volume><issue>3</issue><fpage>930</fpage><lpage>943</lpage><pmc-comment>elocation-id from pubmed: 10.1016/j.celrep.2014.10.008</pmc-comment>
<permissions><copyright-statement>© 2014 The Authors. Published by Elsevier Inc.</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><p id="P1">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 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.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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