PT - JOURNAL ARTICLE AU - Brian Y. H. Lam AU - Irene Cimino AU - Joseph Polex-Wolf AU - Sara Nicole Kohnke AU - Debra Rimmington AU - Valentine Iyemere AU - Nicholas Heeley AU - Chiara Cossetti AU - Reiner Schulte AU - Luis R. Saraiva AU - Darren W. Logan AU - Clemence Blouet AU - Stephen O’Rahilly AU - Anthony P. Coll AU - Giles S. H. Yeo TI - Heterogeneity of hypothalamic Pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing AID - 10.1101/103408 DP - 2017 Jan 01 TA - bioRxiv PG - 103408 4099 - http://biorxiv.org/content/early/2017/01/28/103408.short 4100 - http://biorxiv.org/content/early/2017/01/28/103408.full AB - Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterised simply as direct targets for leptin, recent data suggest a more complex architecture. Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. 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). These data reveal arcuate POMC neurons to be a highly heterogeneous population.