Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing
Objective: Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. Methods: Using single cell RNA sequencing, we have generated an atlas of gene expression i...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-05-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877817300595 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Brian Y.H. Lam Irene Cimino Joseph Polex-Wolf Sara Nicole Kohnke Debra Rimmington Valentine Iyemere Nicholas Heeley Chiara Cossetti Reiner Schulte Luis R. Saraiva Darren W. Logan Clemence Blouet Stephen O'Rahilly Anthony P. Coll Giles S.H. Yeo |
| spellingShingle |
Brian Y.H. Lam Irene Cimino Joseph Polex-Wolf Sara Nicole Kohnke Debra Rimmington Valentine Iyemere Nicholas Heeley Chiara Cossetti Reiner Schulte Luis R. Saraiva Darren W. Logan Clemence Blouet Stephen O'Rahilly Anthony P. Coll Giles S.H. Yeo Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing Molecular Metabolism |
| author_facet |
Brian Y.H. Lam Irene Cimino Joseph Polex-Wolf Sara Nicole Kohnke Debra Rimmington Valentine Iyemere Nicholas Heeley Chiara Cossetti Reiner Schulte Luis R. Saraiva Darren W. Logan Clemence Blouet Stephen O'Rahilly Anthony P. Coll Giles S.H. Yeo |
| author_sort |
Brian Y.H. Lam |
| title |
Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing |
| title_short |
Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing |
| title_full |
Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing |
| title_fullStr |
Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing |
| title_full_unstemmed |
Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing |
| title_sort |
heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell rna sequencing |
| publisher |
Elsevier |
| series |
Molecular Metabolism |
| issn |
2212-8778 |
| publishDate |
2017-05-01 |
| description |
Objective: Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. Methods: Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. Results: Of 163 neurons, 118 expressed high levels of Pomc with little/no Agrp expression and were considered “canonical” POMC neurons (P+). The other 45/163 expressed low levels of Pomc and high levels of Agrp (A+P+). Unbiased clustering analysis of P+ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P+ neurons expressed the leptin receptor (Lepr) compared with 58% (26/45) of A+P+ neurons. In contrast, the insulin receptor (Insr) was expressed at similar frequency on P+ and A+P+ neurons (64% and 55%, respectively). Conclusion: These data reveal arcuate POMC neurons to be a highly heterogeneous population.Accession Numbers: GSE92707. Author Video: Author Video Watch what authors say about their articles Keywords: POMC, Melanocortin, AGRP, Leptin, Insulin, Hypothalamus, Arcuate nucleus, Gene expression, Neuron, Transcriptome |
| url |
http://www.sciencedirect.com/science/article/pii/S2212877817300595 |
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doaj-420acb59b9a143a7bd33fe340d1f7af72020-11-24T23:47:13ZengElsevierMolecular Metabolism2212-87782017-05-0165383392Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencingBrian Y.H. Lam0Irene Cimino1Joseph Polex-Wolf2Sara Nicole Kohnke3Debra Rimmington4Valentine Iyemere5Nicholas Heeley6Chiara Cossetti7Reiner Schulte8Luis R. Saraiva9Darren W. Logan10Clemence Blouet11Stephen O'Rahilly12Anthony P. Coll13Giles S.H. Yeo14MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKFlow Cytometry Core, Cambridge Institute of Medical Research, University of Cambridge, Cambridge CB2 0QQ, UKFlow Cytometry Core, Cambridge Institute of Medical Research, University of Cambridge, Cambridge CB2 0QQ, UKWellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UKWellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UKMRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK; Corresponding author. University of Cambridge Metabolic Research Laboratories, MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Box 289, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.@GilesYeoObjective: Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. Methods: Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. Results: Of 163 neurons, 118 expressed high levels of Pomc with little/no Agrp expression and were considered “canonical” POMC neurons (P+). The other 45/163 expressed low levels of Pomc and high levels of Agrp (A+P+). Unbiased clustering analysis of P+ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P+ neurons expressed the leptin receptor (Lepr) compared with 58% (26/45) of A+P+ neurons. In contrast, the insulin receptor (Insr) was expressed at similar frequency on P+ and A+P+ neurons (64% and 55%, respectively). Conclusion: These data reveal arcuate POMC neurons to be a highly heterogeneous population.Accession Numbers: GSE92707. Author Video: Author Video Watch what authors say about their articles Keywords: POMC, Melanocortin, AGRP, Leptin, Insulin, Hypothalamus, Arcuate nucleus, Gene expression, Neuron, Transcriptomehttp://www.sciencedirect.com/science/article/pii/S2212877817300595 |