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

By Brian Y.H. Lam, Irene Cimino, Joseph Polex-Wolf, Sara Nicole Kohnke, Debra Rimmington, Valentine Iyemere, Nicholas Heeley, Chiara Cossetti, Reiner Schulte, Luis R Saraiva, Darren W. Logan, Clemence Blouet, Stephen O’Rahilly, Anthony Coll, Giles S.H. Yeo

Posted 26 Jan 2017
bioRxiv DOI: 10.1101/103408 (published DOI: 10.1016/j.molmet.2017.02.007)

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.

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