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

Mol Metab. 2017 Mar 1;6(5):383-392. doi: 10.1016/j.molmet.2017.02.007. eCollection 2017 May.


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.

Keywords: AGRP; Arcuate nucleus; Gene expression; Hypothalamus; Insulin; Leptin; Melanocortin; Neuron; POMC; Transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism
  • Animals
  • Cells, Cultured
  • Hypothalamus / cytology*
  • Hypothalamus / metabolism
  • Male
  • Mice
  • Neurons / classification
  • Neurons / metabolism*
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism*
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • Single-Cell Analysis
  • Transcriptome*


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Receptors, Leptin
  • Pro-Opiomelanocortin
  • Receptor, Insulin