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

ABSTRACT: The purpose of this study is to characterize the ontogenetic transcriptional programs that specify the identity and functioning of POMC neurons during early postnatal stage and adulthood. We performed Translating Ribosome Affinity Purification followed by RNA sequencing technology (Trap-seq) using Pomc-CreERT;Rosa26-eGFPL10a transgenic mice where POMC neurons are labeled with eGFPL10a tag with tamoxifen administration. GFP-conjugated beads were used to pull-down POMC neurons from hypothalamic extracts at early postnatal days (P12) and adulthood(P60). Both the pull-down mRNA samples and the resultant supernatant mRNA samples were subjected to RNA sequencing process. Gene enrichment analysis identified 1143 and 1047 genes are highly enriched (P<0.05) in Pomc- eGFPL10a at P12 and P60 Trap-seq materials respectively, from which 653 genes are overlapped expressed in both datasets. Gene ontology analysis showed that these common expressed genes are associated with the establishment and maintenance of neuron structure and basic neuronal functions. The ontology annotations on the uniquely expressed gene from P12 and P60 are dramatically different from each other. The functions of P12 uniquely enriched genes emphasizing on the basic cellular metabolism, cellular modeling and biochemical changes, whereas, the P60 enriched genes are related to the maturation of POMC neurons such neurotransmitter development and POMC specific function establishment including the response to nutrient, and the construction of feeding behavioral circuit.

ORGANISM(S): Mus musculus

PROVIDER: GSE181539 | GEO | 2022/01/28

REPOSITORIES: GEO

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Single cell RNA-seq of the developing mouse hypothalamus

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2021-05-14 | GSE154153 | GEO

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UCP2-dependent redox-sensing in POMC neurons regulates feeding

Project description:Paradoxically, glucose, the primary driver of satiety, activates a small population of anorexigenic POMC neurons. Here we show that lactate levels in the circulation and in the cerebrospinal fluid are elevated in fed state and addition of lactate to glucose activates the majority of POMC neurons while increasing cytosolic NADH generation, mitochondrial respiration and extracellular pyruvate levels. Inhibition of lactate dehydrogenases diminishes mitochondrial respiration, NADH production, and POMC neuronal activity. However, inhibition of the mitochondrial pyruvate carrier has no effect. POMC-specific downregulation of Ucp2 (Ucp2PomcKO), a molecule regulated by fatty acid metabolism and shown to play a role as transporter in the malate-aspartate shuttle, abolishes lactate- and glucose-sensing of POMC neurons. Ucp2PomcKO mice have impaired glucose metabolism and are prone to obesity on a high fat diet. Altogether, our data show that lactate through redox signaling and blocking mitochondrial glucose utilization activates POMC neurons to regulate feeding and glucose metabolism.

2022-11-28 | ST002361 | MetabolomicsWorkbench

Microglial transcriptome of Maternal Immune Activation model at different developmental Stages and after microglia repopulation

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