ECEESPE2025 Oral Communications Oral Communications 9: Endocrine Related Cancer (5 abstracts)
Genetic and functional heterogeneity in aldosterone producing adenomas
Maria Maldifassi 1,2 , Jiayi Wang 3 , David Colameo 1 , Qin Zhang 4 , Anna Bratus-Neuenschwander 4 , Agnieszka Wengi 5 , Hubert Rehrauer 4 , Igor Delvendahl 6 , Mark Robinson 3 , Felix Beuschlein 7 & David Penton Ribas 1
1University of Zurich, Electrophysiology Facility, Zurich, Switzerland; 2University of Zurich, Electrophysiology Facility, Zurich, Switzerland; 3University of Zurich, Department of Molecular Life Sciences, Zurich, Switzerland; 4University of Zurich, Functional Genomics Center Zurich, Zurich, Switzerland; 5University Hospital Zurich, Department of Endocrinology, Diabetology and Clinical Nutrition, Schlieren, Switzerland; 6University of Freiburg, Institute of Physiology, Freiburg im Breisgau, Germany; 7University Hospital Zurich, Department of Endocrinology, Diabetology and Clinical Nutrition, Zurich, Switzerland
JOINT1268
Primary aldosteronism (PA), the most common secondary form of hypertension, results from excessive and autonomous aldosterone production by the adrenal cortex. Gain-of-function mutations in genes encoding ion channels or transporters underlie both inherited and acquired forms of PA. These mutations typically promote cell depolarization and increase intracellular Ca2+ levels, driving the overexpression and activity of the aldosterone synthase. Cellular heterogeneity is thought to be an intrinsic feature of PA, modulating its presentation and severity. However, understanding this complexity at the single-cell level has been challenging due to the limitations of traditional methods and lack of functional read-outs. To overcome this, we have combined single-cell long-read RNA sequencing (scRNA-seq), PatchSeq and high-throughput automated patch-clamp (HT-APC) techniques. This approach was applied to freshly dissociated cells from adrenal tissues resected from patients with aldosterone-producing adenomas (APA) or adrenal hyperplasia at the University Hospital Zurich. Preliminary analysis of 2,177 adrenocortical cells from seven patient samples (from normal, tumor and hyperplasia tissues) revealed over 100 likely pathogenic variants, as per ClinVar. These include known PA-driver mutations in KCNJ5, CLCN2, CACNA1D, and CACNA1H, along with novel mutations in potential steroidogenesis-related genes such as WNK1, VDR, PEX1, and KCNJ1. Interestingly, some genetic variants co-occur with known PA-driver mutations, offering insights into the one- or two-hit models of APA development. For future functional analysis, we have developed an automated pipeline that integrates high-content imaging with HT-APC electrophysiological data to identify recorded cells using steroidogenesis markers. The use of PatchSeq enables correlation of cellular functional data with mutation status and transcriptomic profiles, contextualizing the datasets derived from scRNA-seq and HT-APC. Additionally, transcriptomic analysis is anticipated to uncover novel cell markers associated with increased steroidogenesis. This innovative approach provides a detailed understanding of PA’s molecular and functional heterogeneity at the single-cell level. The tools developed in this study could be broadly applied to other tissues where alterations in electrophysiological properties drive disease progression.
Volume 110
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2025 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more