Biology subjects

Sarvari, M.

Publications and source records attributed to Sarvari, M..

4 recordsLinked to original sources

bioRxiv2025

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

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.

neuroscience↗

bioRxiv2023

Estrogen-dependent development and transcriptome regulation of the lateral septal kisspeptin system

While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KPLS) neurons of the lateral septum. Our studies on Kiss1-Cre/ZsGreen transgenic mice revealed that KP expression in the LS is linked to puberty and estrogen receptor signaling and neurons reach higher numbers in females. Viral tracing uncovered that KPLS axons abundantly innervate gonadotropin-releasing hormone neurons, the hypothalamic supramammillary nucleus and various limbic structures. RNA-Seq analysis of laser-microdissected KPLS neurons revealed a unique transcriptome profile containing markers of GABAergic and peptidergic (Penk, Cartpt, Vgf) cotransmission and 571 estrogen-dependent transcripts. Immunohistochemical evidence for homologous neurons in the post mortem human brain indicate that the KPLS neurons may contribute to evolutionarily conserved regulatory mechanisms. The KPLS system now emerges as a novel player in the estrogen-dependent control of gonadotropin-releasing hormone neurons and currently unknown hypothalamic and limbic functions requiring clarification.

neuroscience↗

bioRxiv2023

Development of a versatile LCM-Seq method for spatial transcriptomics of fluorescently-tagged cholinergic neuron populations

Single-cell transcriptomics are powerful tools to define neuronal cell types based on co-expressed gene clusters. Limited RNA input in these technologies necessarily compromises transcriptome coverage and accuracy of differential expression analysis. We propose that bulk RNA-sequencing of neuronal pools defined by spatial position offers an alternative strategy to overcome these technical limitations. We report an LCM-Seq method which allows deep transcriptome profiling of fluorescently-tagged neuron populations isolated with laser-capture microdissection (LCM) from histological sections of transgenic mice. Mild formaldehyde-fixation of ZsGreen marker protein, LCM sampling of [~]300 pooled neurons, followed by RNA isolation, library preparation and RNA-sequencing with methods optimized for nanogramm amounts of moderately degraded RNA enabled us to detect [~]15,000 different transcripts in fluorescently-labeled cholinergic neuron populations. The versatile LCM-Seq method showed excellent accuracy in quantitative studies, with 2,891 transcripts expressed differentially between the spatially defined and clinically relevant cholinergic neuron populations of the caudate-putamen and medial septum.

neuroscience↗

bioRxiv2021

The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia

Human reproduction is controlled by [~]2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional 150-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Extrahypothalamic GnRH neurons were cholinergic. Though undetectable in adult rodents, the GnRH-GFP transgene was expressed transiently by caudate-putamen cholinergic interneurons in newborn transgenic mice. In slice electrophysiological studies, GnRH inhibited these interneurons via GnRHR1 autoreceptors. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen confirmed selective expression of GNRH1 and GNRHR1 autoreceptors in cholinergic cells and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher- order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. GnRH/GnRHR1 signaling as a potential therapeutic target in the treatment of neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinsons and Alzheimers diseases, needs to be explored.

cell biology↗