Searchable abstracts of presentations at key conferences in endocrinology

ea0092op-02-02 | Oral Session 2: Thyroid hormone action in the brain | ETA2023

Development of an image-based method for spatial registration of T3-induced changes in cell types and gene expression in human cerebral organoids

Bresser Audrey , Obermayer-Wasserscheid Benedikt , Megges Matthias , Fernandez-Vallone Valeria , Stachelscheid Harald , Kuhnen Peter , Opitz Robert

Thyroid hormone (TH) signaling is essential for nervous system development. The clinical relevance of this simple statement is underscored by the severe neurological phenotypes resulting from global TH deficiency or perturbed local TH signaling during fetal development. A major aim of our research is to better understand the local action of TH during early human cortex development using cerebral organoids derived from human induced pluripotent stem cells (hiPSC) as a model sys...

ea0101op-01-06 | Oral Session 1: Topic Highlights | ETA2024

Cut&tag reveals distinct TRA2-specific DNA binding profiles in HIPSC-derived cardiomyocytes

Harting Nina , Ludwik-Shah Katarzyna , Stachelscheid Harald , Surowy Harald , Kilpert Fabian , Koster Johannes , Kaiser Frank J.

Objective: Thyroid hormone receptors (TRs) are important ligand-dependent regulators of thyroid hormone target gene expression. In contrast, the role of TRα2, a thyroid hormone receptor α splice variant that is unable to bind thyroid hormones, remains enigmatic for more than 30 years. However, its evolutionary conservation in eutherian mammals and high expression levels in some cell types as well as under ‘pathological conditions’ such as heart failure stro...

ea0101ps2-10-10 | Intracellular effects of TH | ETA2024

Impact of triiodothyronine (T3) on differentiation and T3-responsive characteristics in ipsc-derived hepatocyte-like cells to study energy and lipid metabolism

Seifert Joshua , Ludwik-Shah Katarzyna , von Kugelgen Nicolai , Jahn Regina , Kohrle Josef , Stachelscheid Harald , Wirth Eva

Background: The increasing global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes its significant health implications, including liver inflammation, cirrhosis, and malignancy. Thyroid hormones (TH) play a vital role in hepatic energy metabolism, and their reduced local availability in the liver is associated with MASLD development. This study presents the comprehensive characterization of functional components of the TH system in human...

ea0084op-13-67 | Oral Session 13: Basic 3 | ETA2022

A single cell atlas of the T3-responsive transcriptome during early cortical neurogenesis in human cerebral organoids

Opitz Robert , Fernandez-Vallone Valeria , Megges Matthias , Amber Julie Bresser Audrey , Obermayer-Wasserscheid Benedikt , Stachelscheid Harald , Kuhnen Peter

Perturbation of thyroid hormone (TH) function during prenatal brain development can cause a spectrum of neurological disorders as evident in pediatric patients with untreated congenital hypothyroidism or patients with mutations in THRA and SLC16A2 genes. However, scarcity and inaccessibility of human brain tissue from early developmental stages has been a major roadblock for experimental approaches to decipher local TH action in early development. Advanced <e...

ea0084ps1-02-18 | Hypothyroidism | ETA2022

Human cerebral organoids as in vitro platform to assess thyroid hormone system disrupting chemicals

Fernandez-Vallone Valeria , Hellwig Lina , Opitz Robert , Obermayer-Wasserscheid Benedikt , Wiese Niklas , Rijntjes Eddy , Kohrle Josef , Mergenthaler Philipp , Stachelscheid Harald

Thyroid hormones (TH) play a fundamental role in brain development. Changes on TH availability during pregnancy and early childhood can lead to neurological disorders. Accordingly, concerns are mounting that exposure to environmental compounds capable of interfering with TH action can disrupt neuronal development. Current approaches to categorize chemicals as thyroid hormone system disrupting chemicals (THSDC) are mainly based on determination of changes in circulating TH conc...

ea0084ps1-04-35 | Thyroid Hormone Transporters and Development | ETA2022

Spatiotemporal expression of the thyroid hormone transporter MCT8 during cortical neurogenesis in human cerebral organoids

Graffunder Adina , Amber Julie Bresser Audrey , Anthofer Larissa , Megges Matthias , Fernandez-Vallone Valeria , Stachelscheid Harald , Kuhnen Peter , Opitz Robert

Thyroid hormones (TH) play a critical role during nervous system development and patients carrying coding variants of THRA or SLC16A2/MCT8 genes present a spectrum of neurological phenotypes presumably resulting from perturbed local TH action during early brain development. Monocarboxylate transporter MCT8 is a well-characterized TH membrane transporter and MCT8 mutations have been associated with the Allan-Herndon-Dudley Syndrome. Recent advances in stem cel...

ea0084ps2-09-81 | Thyroid Hormone ACTION | ETA2022

An experimental framework for probing molecular mechanisms of local thyroid hormone action during cortical neurogenesis in human cerebral organoids

Amber Julie Bresser Audrey , Graffunder Adina , Anthofer Larissa , Megges Matthias , Obermayer-Wasserscheid Benedikt , Rijntjes Eddy , Wiese Niklas , Fernandez-Vallone Valeria , Stachelscheid Harald , Kuhnen Peter , Opitz Robert

Recently, human cerebral organoids (hCOs) emerged as powerful three-dimensional in vitro models recapitulating key aspects of early human cerebral cortex development. Improved protocols for hCO generation from induced pluripotent stem cells (hiPSC) paved the way for new disease modeling approaches and enable multimodal analyses of perturbed neurogenesis resulting from manipulation of signaling pathways or gene function. These prospects prompted us to adopt this techno...