Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing

Brian Y.H. Lam, Irene Cimino, Joseph Polex-Wolf, Sara Nicole Kohnke, Debra Rimmington, Valentine Iyemere, Nicholas Heeley, Chiara Cossetti, Reiner Schulte, Luis Miguel Rodrigues Saraiva, Darren W. Logan, Clemence Blouet, Stephen O'Rahilly, Anthony P. Coll, Giles S.H. Yeo

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)383-392
Number of pages10
JournalMolecular Metabolism
Volume6
Issue number5
DOIs
Publication statusPublished - 1 May 2017
Externally publishedYes

Fingerprint

RNA Sequence Analysis
Pro-Opiomelanocortin
Neurons
Leptin Receptors
Atlases
Insulin Receptor
Cell Surface Receptors
Leptin
Transcriptome
Cluster Analysis
Body Weight
Gene Expression

Keywords

  • AGRP
  • Arcuate nucleus
  • Gene expression
  • Hypothalamus
  • Insulin
  • Leptin
  • Melanocortin
  • Neuron
  • POMC
  • Transcriptome

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Lam, B. Y. H., Cimino, I., Polex-Wolf, J., Nicole Kohnke, S., Rimmington, D., Iyemere, V., ... Yeo, G. S. H. (2017). Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. Molecular Metabolism, 6(5), 383-392. https://doi.org/10.1016/j.molmet.2017.02.007

Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. / Lam, Brian Y.H.; Cimino, Irene; Polex-Wolf, Joseph; Nicole Kohnke, Sara; Rimmington, Debra; Iyemere, Valentine; Heeley, Nicholas; Cossetti, Chiara; Schulte, Reiner; Rodrigues Saraiva, Luis Miguel; Logan, Darren W.; Blouet, Clemence; O'Rahilly, Stephen; Coll, Anthony P.; Yeo, Giles S.H.

In: Molecular Metabolism, Vol. 6, No. 5, 01.05.2017, p. 383-392.

Research output: Contribution to journalArticle

Lam, BYH, Cimino, I, Polex-Wolf, J, Nicole Kohnke, S, Rimmington, D, Iyemere, V, Heeley, N, Cossetti, C, Schulte, R, Rodrigues Saraiva, LM, Logan, DW, Blouet, C, O'Rahilly, S, Coll, AP & Yeo, GSH 2017, 'Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing', Molecular Metabolism, vol. 6, no. 5, pp. 383-392. https://doi.org/10.1016/j.molmet.2017.02.007
Lam, Brian Y.H. ; Cimino, Irene ; Polex-Wolf, Joseph ; Nicole Kohnke, Sara ; Rimmington, Debra ; Iyemere, Valentine ; Heeley, Nicholas ; Cossetti, Chiara ; Schulte, Reiner ; Rodrigues Saraiva, Luis Miguel ; Logan, Darren W. ; Blouet, Clemence ; O'Rahilly, Stephen ; Coll, Anthony P. ; Yeo, Giles S.H. / Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. In: Molecular Metabolism. 2017 ; Vol. 6, No. 5. pp. 383-392.
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abstract = "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.",
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AU - Rimmington, Debra

AU - Iyemere, Valentine

AU - Heeley, Nicholas

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AU - Rodrigues Saraiva, Luis Miguel

AU - Logan, Darren W.

AU - Blouet, Clemence

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N2 - 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.

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