Developmental single-cell transcriptomics of hypothalamic POMC neurons reveal the genetic trajectories of multiple neuropeptidergic phenotypes
Abstract
Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus are essential to regulate food intake and energy balance. However, the ontogenetic transcriptional programs that specify the identity and functioning of these neurons are poorly understood. Here, we use scRNAseq to define the transcriptomes characterizing Pomc-expressing cells in the developing hypothalamus and TRAP-seq to analyze the subsequent translatomes of mature POMC neurons. Our data showed that Pomc-expressing neurons give rise to multiple developmental pathways expressing different levels of Pomc and unique combinations of transcription factors. The predominant cluster, featured by high levels of Pomc and Prdm12 transcripts represents the canonical arcuate POMC neurons. Additional cell clusters expressing medium or low levels of Pomc mature into different neuronal phenotypes featured by distinct sets of transcription factors, neuropeptides, processing enzymes, cell surface and nuclear receptors. We conclude that the genetic programs specifying the identity and differentiation of arcuate POMC neurons are diverse and generate a heterogeneous repertoire of neuronal phenotypes early in development that continue to mature postnatally.
Data availability
All raw data have been deposited in the Gene Expression Omnibus under accession numbers GSE154153 and GSE181539.
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Single cell RNA-seq of the developing mouse hypothalamusNCBI Gene Expression Omnibus, GSE154153.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (DK068400)
- Malcolm J Low
National Institute of Diabetes and Digestive and Kidney Diseases (DK068400)
- Marcelo Rubinstein
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were performed in accordance with the Institutional Animal Care and Use Committee (IACUC) protocol (PRO00008570) at the University of Michigan and followed the Public Health Service guidelines for the humane care and use of experimental animals.
Copyright
© 2022, Yu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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