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Mol Metab. 2017 Mar 1;6(5):383-392. doi: 10.1016/j.molmet.2017.02.007. eCollection 2017 May.

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

Author information

1
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
2
Flow Cytometry Core, Cambridge Institute of Medical Research, University of Cambridge, Cambridge CB2 0QQ, UK.
3
Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
4
MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: gshy2@cam.ac.uk.

Abstract

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.

KEYWORDS:

AGRP; Arcuate nucleus; Gene expression; Hypothalamus; Insulin; Leptin; Melanocortin; Neuron; POMC; Transcriptome

PMID:
28462073
PMCID:
PMC5404100
DOI:
10.1016/j.molmet.2017.02.007
[Indexed for MEDLINE]
Free PMC Article

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