Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing
Authors
Cimino, I
Polex-Wolf, J
Nicole Kohnke, S
Rimmington, D
Iyemere, V
Heeley, N
Cossetti, C
Schulte, R
Saraiva, LR
Logan, DW
Publication Date
2017-05-01Journal Title
Molecular Metabolism
ISSN
2212-8778
Publisher
Elsevier
Volume
6
Issue
5
Pages
383-392
Language
English
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Lam, B., Cimino, I., Polex-Wolf, J., Nicole Kohnke, S., Rimmington, D., Iyemere, V., Heeley, N., et al. (2017). Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing. Molecular Metabolism, 6 (5), 383-392. https://doi.org/10.1016/j.molmet.2017.02.007
Abstract
$\textbf{Objective}$
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.
$\textbf{Methods}$
Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons.
$\textbf{Results}$
Of 163 neurons, 118 expressed high levels of $\textit{Pomc}$ with little/no Agrp expression and were considered “canonical” POMC neurons (P$^{+}$). The other 45/163 expressed low levels of $\textit{Pomc}$ and high levels of $\textit{Agrp}$ (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 ($\textit{Lepr}$) compared with 58% (26/45) of A$^{+}$P$_{+}$ neurons. In contrast, the insulin receptor ($\textit{Insr}$) was expressed at similar frequency on P$^{+}$ and A$^{+}$P$_{+}$ neurons (64% and 55%, respectively).
$\textbf{Conclusion}$
These data reveal arcuate POMC neurons to be a highly heterogeneous population. Accession Numbers: GSE92707.
Keywords
POMC, melanocortin, AGRP, leptin, insulin, hypothalamus, arcuate nucleus, gene expression, neuron, transcriptome
Sponsorship
This work was supported by the UK Medical Research Council (MRC) Metabolic Disease Unit (MRC_MC_UU_12012/1 & MRC_MC_UU_12012/5), a Wellcome Trust Strategic Award (100574/Z/12/Z), and the Helmholtz Alliance ICEMED.
Funder references
MRC (MC_UU_12012/1)
MRC (MC_UU_12012/5)
BBSRC (1644127)
Wellcome Trust (100574/Z/12/Z)
MEDICAL RESEARCH COUNCIL (G0900554)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.1016/j.molmet.2017.02.007
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264134
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International