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

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45 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

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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., Heeley, N., Cossetti, C., Schulte, R., Rodrigues Saraiva, L. M., Logan, D. W., Blouet, C., O'Rahilly, S., Coll, A. P., & 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