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 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.