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

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 with little/no expression and were considered "canonical" POMC neurons (P). The other 45/163 expressed low levels of and high levels of (AP). 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 () compared with 58% (26/45) of AP neurons. In contrast, the insulin receptor () was expressed at similar frequency on P and AP neurons (64% and 55%, respectively).

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