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bioRxiv · 10.1101/2025.08.19.671088

Deep transcriptome profiling of human hypothalamic agouti-related protein and proopiomelanocortin neurons regulating energy homeostasis

Takacs, S. F.·Skrapits, K.·Göcz, B.·Rumpler, E.·Sarvari, M.·Poliska, S.·Racz, G.·Matolcsy, A.·Hrabovszky, E.
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Abstract

We have developed and validated a pioneering IHC/LCM-Seq method for transcriptome profiling of spatially defined neuronal cell types detected with immunohistochemistry in sections of formaldehyde-fixed human brains. IHC/LCM-Seq provided unprecedented insight, with 14,000-16,000 transcripts identified, into the gene expression landscape of human agouti-related peptide (AgRP) neurons, which drive appetite and energy storage, and proopiomelanocortin (POMC) neurons, which suppress feeding and promote energy expenditure. These cells differed from each other, and from fertility-regulating kisspeptin neurons, in their distinct enrichments of co-transmitters, transcription factors, and receptors. The AgRP neuron transcriptome was rich in receptors for proinflammatory cytokines, metabolic hormones and growth hormone, whereas POMC neurons expressed reproductive hormone-, glucagon-like peptide- and endocannabinoid receptors. IHC/LCM-Seq, a versatile spatial transcriptomic approach for characterizing cell types in postmortem brains, opened a new window onto molecular mechanisms regulating energy homeostasis in the human hypothalamus and highlighted possible pharmacological targets for weight management.

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Takacs, S. F., Skrapits, K., Göcz, B., Rumpler, E., Sarvari, M., Poliska, S., Racz, G., Matolcsy, A., Hrabovszky, E.. 2025-08-19. Deep transcriptome profiling of human hypothalamic agouti-related protein and proopiomelanocortin neurons regulating energy homeostasis. https://doi.org/10.1101/2025.08.19.671088

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