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

Abstract

$\textbf{Objective}$

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.

$\textbf{Methods}$

Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons.

$\textbf{Results}$

Of 163 neurons, 118 expressed high levels of $\textit{Pomc}$ with little/no Agrp expression and were considered “canonical” POMC neurons (P$^{+}$). The other 45/163 expressed low levels of $\textit{Pomc}$ and high levels of $\textit{Agrp}$ (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 ($\textit{Lepr}$) compared with 58% (26/45) of A$^{+}$P$_{+}$ neurons. In contrast, the insulin receptor ($\textit{Insr}$) was expressed at similar frequency on P$^{+}$ and A$^{+}$P$_{+}$ neurons (64% and 55%, respectively).

$\textbf{Conclusion}$

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