Researchers developed a spatial transcriptomic method called IHC/LCM-Seq to profile specific neuronal cell types in formaldehyde-fixed human brain tissue, according to a study published in Nature Communications.
Applying the technique to male human hypothalami, the research team identified 14,000 to 16,000 transcripts in agouti-related protein (AgRP) neurons and proopiomelanocortin (POMC) neurons. AgRP neurons drive appetite and promote energy storage, while POMC neurons suppress feeding and promote energy expenditure.
The profiling showed distinct molecular differences between the two cell types, as well as distinctions from fertility-regulating kisspeptin neurons. These differences appeared across regulatory long non-coding RNAs, co-transmitters, transcription factors, and cell receptors.
AgRP neurons showed an enrichment of receptors for metabolic hormones, growth hormone, and proinflammatory cytokines. POMC neurons instead expressed receptors for glucagon-like peptides, reproductive hormones, calcitonin, and endocannabinoids. The researchers noted that these molecular profiles highlight potential pharmacological targets for weight-management treatments.
Szabolcs Takács and Katalin Skrapits contributed equally to the study alongside co-authors from the Hun-Ren Institute of Experimental Medicine, Pázmány Péter Catholic University, the University of Debrecen, and Semmelweis University. The research was funded by the National Research, Development and Innovation Office under grants 152847, 152320, and PD134837, with study antibodies supplied by Drs. C. Fekete, W.S. Dhillo, P. Ciofi, and J.T. Clausen.
