Developmental single-cell transcriptomics of hypothalamic POMC neurons reveal the genetic trajectories of multiple neuropeptidergic phenotypes

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 single-cell RNA-sequencing...

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Bibliographic Details
Published in:eLife 2022-01, Vol.11
Main Authors: Yu, Hui, Rubinstein, Marcelo, Low, Malcolm J
Format: Article
Language:English
Subjects:
Animals
Approximation
Arcuate nucleus
Cell surface
Cluster analysis
development
Developmental Biology
Energy balance
Food intake
Gene expression
Genomics
Hypothalamus
Hypothalamus - metabolism
Mice
Neurogenesis
Neurons - metabolism
Neuropeptides
Neuroscience
Nuclear receptors
Ontogeny
Phenotype
Phenotypes
POMC
Pro-Opiomelanocortin - metabolism
Proopiomelanocortin
RNA-Seq
Single-Cell Analysis
single-cell transcriptomics
Tools and Resources
Transcription factors
Transcriptome
Transcriptomes
Transcriptomics
Transgenic animals
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Summary: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 single-cell RNA-sequencing (scRNA-seq) to define the transcriptomes characterizing -expressing cells in the developing hypothalamus and translating ribosome affinity purification with RNA-sequencing (TRAP-seq) to analyze the subsequent translatomes of mature POMC neurons. Our data showed that -expressing neurons give rise to multiple developmental pathways expressing different levels of and unique combinations of transcription factors. The predominant cluster, featured by high levels of and transcripts, represents the canonical arcuate POMC neurons. Additional cell clusters expressing medium or low levels of 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.72883