Elsevier

Molecular Metabolism

Volume 6, Issue 5, May 2017, Pages 383-392
Molecular Metabolism

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

https://doi.org/10.1016/j.molmet.2017.02.007Get rights and content
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Highlights

  • Hypothalamic POMC neurons are heterogeneous and can broadly divided into 4 groups.

  • Cell surface receptors are major drivers for the segregation.

  • Unexpectedly, 28% of POMC-cells show signatures typical of AgRP/NPY neurons.

  • Only 12% express leptin receptor, indicating response to leptin is likely indirect.

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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Keywords

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

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