PhD Scientific Days 2025

Poster Session I. - Q: Neurosciences

Single-nucleus transcriptome analysis of the human arcuate nucleus

Előadó neve

Dr. Dóra Fanni

Neptun code

Z1WZFL

Előadó munkahelye

Semmelweis University, Department of Anatomy, Histology| and Embryology

Előadó telefonszáma

+36306911544

Előadó e-mail címe

dora.fanni@semmelweis.hu

Az előadás címe

Single-nucleus transcriptome analysis of the human arcuate nucleus

Szerző(k) neve és munkahelye

Fanni Dóra¹, Éva Renner¹, Alán Alpár¹, Miklós Palkovits¹, Árpád Dobolyi²

1: Semmelweis University, Human Brain Tissue Bank, Budapest, Hungary
2: Eötvös Loránd University, Department of Physiology and Neurobiology, Laboratory of Molecular and Systems Neurobiology, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session I. - Q: Neurosciences

Language of the presentation

Hungarian

Preferred session

Neurosciences

Összefoglaló szövege

Introduction
The arcuate nucleus (AN) of the mediobasal hypothalamus plays a central role in endocrine and metabolic regulation via diverse neuronal populations, including POMC, AgRP, GHRH, TIDA, and KNDy neurons. Despite their importance, the molecular identity, heterogeneity, and spatial organization of human AN neurons remain poorly defined.

Aims
We aimed to generate a comprehensive single-nucleus transcriptomic atlas of the human AN to uncover its cellular diversity, neurotransmitter and neuropeptide profiles, and intercellular communication pathways.

Methods
We performed single-nucleus RNA sequencing (snRNA-seq) on pooled postmortem hypothalamic tissue containing the AN from eight neurologically healthy adult donors. Following quality control, dimensionality reduction, and clustering, we identified major cell types and focused on neurons. Differential gene expression analysis defined neurotransmitter phenotypes. Neuronal subpopulations were further resolved by subclustering, and neuropeptide expression was analyzed to explore functional diversity. Ligand-receptor interaction analysis was used to infer intercellular communication networks.

Results
snRNA-seq revealed 22 distinct cell clusters in the human AN, including glial, and ependymal cells. Neurons were predominantly GABAergic, with smaller glutamatergic subsets. Neuronal subclustering identified 23 distinct subpopulations with diverse neurotransmitter and neuropeptide profiles. Neuropeptides such as TRH, and NPPC showed cluster-specific expression, suggesting novel neuronal types. Ligand-receptor analysis revealed extensive signaling, notably involving TAC3–IGFBP3, and CRHR2–PTH2R expressing neurons. These findings establish the first detailed transcriptomic map of the human AN, highlighting its molecular heterogeneity and intercellular communication.

Conclusion
This study presents the first comprehensive single-nucleus transcriptomic map of the human AN, revealing its cellular diversity and cell-cell communication networks. These insights advance our understanding of hypothalamic regulation and may inform new therapeutic strategies.

Funding
Supported by HAS NAP3 (NAP2022-I-3/2022, NAP2022-I-4/2022), NKFIH grants K146077 and 151425, TKP2021-EGA-25, and EKÖP-2024-00004, funded by the Ministry for Culture and Innovation via the NKFIH.

University

Semmelweis University

Supervisor

Prof. Árpád Dobolyi

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8040

Start

17:18

End

17:24