$Objective$

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$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$). The other 45/163 expressed low levels of $Pomc$ and high levels of $Agrp$ (A$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$P$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$). Unbiased clustering analysis of P$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$ neurons expressed the leptin receptor ($Lepr$) compared with 58% (26/45) of A$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$P$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$ neurons. In contrast, the insulin receptor ($Insr$) was expressed at similar frequency on P$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$ and A$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$P$\mathrm{<mrow\; data-mjx-texclass="ORD">+</mrow>}$ neurons (64% and 55%, respectively).

$Conclusion$

These data reveal arcuate POMC neurons to be a highly heterogeneous population. Accession Numbers: GSE92707.