26.04.2026, Sunday, 12:30-14:00
General focus of the symposium:
Human cellular models have opened new avenues for understanding the mechanisms that shape brain physiology and contribute to neurological and psychiatric disorders. This symposium will gather researchers who employ iPSC-based models, direct reprogramming strategies, and emerging 3D systems to study human neural development, stress responsiveness, and disease-related processes in a biologically relevant context. By combining diverse methodological perspectives, the session aims to highlight how human-derived models are redefining experimental possibilities in neuroscience.
A central focus of the symposium is how these platforms capture features that are difficult to reproduce in traditional systems, including human genetic background, regulatory complexity, and aspects of maturation or aging. Talks will examine how molecular pathways are regulated in human neural cells, how they respond to environmental or hormonal stimuli, and how these responses may contribute to vulnerability or resilience across different conditions. Another key theme is the translational potential of these approaches. Presentations will illustrate how human cellular systems can reveal mechanisms relevant to neurodevelopmental, psychiatric, and neurodegenerative disorders, and how they may support the identification of new therapeutic targets. By emphasizing conceptual advances and methodological innovation, the symposium will encourage discussion on the strengths and limitations of human-based modeling, as well as on how these systems can be integrated with complementary technologies.
Overall, this session aims to provide a broad and forward-looking perspective on how human cellular approaches are shaping contemporary neuroscience and enabling new strategies for investigating the biological foundations of brain health and disease.
12:30 Dr. Cristiana Cruceanu
Karolinska Institutet, Department of Physiology and Pharmacology
"Stress and Cortical Development: Cellular and Gene Regulatory Pathways in Neurodevelopmental Disorders"
Dr. Cruceanu will discuss the work of the Developmental and Translational Neurobiology research group, which she leads at the Karolinska Institutet in Stockholm, Sweden.
Motivated by the developmental origins of health and disease hypothesis, she will show data aiming to elucidate how prenatal environment exposures can shape fetal neurodevelopment.
State-of-the-art approaches using longitudinal human cohorts, population health register data, and in-vitro and ex-vivo model systems and single-cell multi-omics, will investigate the molecular responses and implications of exposure to stress hormones and synthetic glucocorticoids as well as psychotropic medications, especially selective serotonin reuptake inhibitors.
Converging lines of evidence will concentrate on the effect of these exposures in the most important human tissues along the maternal-fetal interface: the brain and the placenta.
Important implications of studying molecular mechanisms in human-specific models will be discussed.
13:10 Viorica Raluca Contu
Biology of Astrocytes Research Group, Life Science and Biotechnology Center, Łukasiewicz Research Network – PORT Polish Center for Technology Development, Wroclaw, Poland
"Decoding Stress Hormone Signaling in the Human Brain Using iPSC-derived Neural Cells"
Stress is a major risk factor for a wide range of psychiatric disorders, yet the molecular mechanisms through which stress hormones affect the human brain remain incompletely understood. Glucocorticoids (GCs) mediate the stress response primarily through the glucocorticoid receptor (GR), a transcription factor that operates in a tissue- and cell-specific manner. While GR-regulated pathways are well characterized in peripheral organs, the effects of GCs in brain cells are less clear.
Here, we investigated GR signaling in a human-relevant system using surface-attached 3D mixed neural cultures derived from iPSCs.
Cultures were exposed to cortisol or the synthetic GR agonist dexamethasone, followed by whole-transcriptome sequencing in addition to targeted analyses using immunocytochemistry and qPCR.
Our results reveal robust activation of canonical GR bona fide genes across neural populations, alongside distinct cell-type- and treatment-specific components of the response. These findings highlight heterogeneity in GR signaling within human neural systems and suggest that differential transcriptional responses may contribute to stress-related vulnerability or resilience.
Overall, this work provides insight into how stress hormones shape molecular programs in the human brain and offers a framework for studying mechanisms relevant to stress-related psychiatric disorders and therapeutic target discovery.
13:23 Karolina Cierluk
Łukasiewicz Research Network - PORT Polish Center for Technology Development, Mechanisms of Neurodegeneration Group; Wroclaw Medical University
"Investigation of Age-Associated Neurodegenerative Phenotypes in Directly Converted Human Neurons"
Neurodegenerative diseases (NDDs) are devastating, age-associated disorders characterized by progressive neuronal loss that, despite extensive research efforts, remain largely incurable. Impairment of protein quality control (PQC) is a central pathogenic feature of NDDs, promoting the accumulation of misfolded pathogenic proteins and progressive cellular dysfunction. Notably, PQC efficiency declines with age, the strongest risk factor for neurodegeneration.
Translational research in NDDs has proven challenging because many traditional experimental models have failed to accurately recapitulate the complexity of human disease mechanisms, limiting their predictive and translational value. The implementation of cell reprogramming methods has opened a new era in research and enabled modeling NDD in the context of human genetics.
In our research, we use human models derived from patients to study the molecular mechanisms of NDDs. Through the implementation of direct-reprogramming methods, which omit the pluripotent stage, cells retain the transcriptional and epigenetic signatures of the donors cells which allow us to study NDDs mechanisms in the context of aging.
In this aging-relevant environment we investigate the mechanisms of PQC decline and search for modifiers of age-relevant disease phenotypes. The implementation of the neuron-astrocyte co-culture systems enables us to investigate how protein homeostasis in astrocytes contributes to the development of neuronal dysfunctions.
With this translational approach, we hope to reveal aging-relevant molecular mechanisms underlying neurodegenerative pathology both in neurons and astrocytes and discover factors to be further explored for therapeutic purposes in NDDs.
13:36 Erkan Metin
Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute Polish Academy of Sciences
"Organoid Biobanks for Neurodevelopmental Vulnerability: a Mitochondrial Perspective"
Early human neurodevelopment involves dynamic changes in mitochondrial function. In brain organoid cultures, variability between independent differentiation experiments and batches can make it difficult to compare equivalent developmental stages across different genetic backgrounds. Establishing reliable cryopreservation methods for patient-derived organoids may help preserve defined developmental time points and enable more consistent analysis of mitochondrial changes during early human neurodevelopment.
This study aimed to evaluate different cryopreservation strategies in patient-derived ventral forebrain organoids and to determine how these methods influence early post-thaw recovery and downstream mitochondrial analyses.
Human ventral forebrain organoids were generated from induced pluripotent stem cells, including both non-disease reference lines and Dravet syndrome patient-derived lines. Organoids were cryopreserved using Cryostor and MEDY on day 18 of differentiation and assessed one and two weeks after thawing. Post-thaw recovery was evaluated by measuring organoid size and morphology, examining ventral forebrain progenitor and early neuronal markers using immunocytochemistry, and performing metabolic and viability assays.
We observed clear method-dependent differences in early recovery after cryopreservation. The CryoStor-based method preserved organoid architecture and growth consistency more effectively than the MEDY-based approach, which showed reduced structural stability during early recovery. Ongoing analyses are assessing whether these structural differences are associated with changes in mitochondrial activity and developmental marker expression in both disease and reference organoids.
These findings indicate that standardized cryopreservation improves experimental control by preserving defined developmental stages and enabling more reliable comparisons between disease and reference organoids when investigating early mitochondrial regulation.
13:49 Victoria Graffe
Mossakowski Medical Research Institute, Polish Academy of Sciences, Department of Stem Cell Bioengineering, Huntington's Disease Group
"Unraveling Huntington's Disease Using Human iPSC-derived Models"
Huntington's Disease (HD) is an inherited motor, cognitive and psychiatric disorder that currently has no cure. Although HD has been primarily addressed as a neurodegenerative disease, alterations in early developmental stages in both adult and juvenile onsets suggest that HD could have a neurodevelopmental origin.
Our aim is to use induced Pluripotent Stem Cells (iPSC) to generate 2D and 3D in vitro models that can serve as platforms to recapitulate neurodevelopment in HD and identify pathological mechanisms behind it.
Transfection of dermal fibroblasts with OCT4, SOX2, KLF4, and C-MYC to generate iPSC lines, differentiation of such lines into 2D neural progenitor cells (NPCs) and medium spiny neurons (MSNs), as well as 3D cortical and striatal organoids. Characterization of iPSC lines and iPSC-derived models through immunofluorescence, PCR and transcriptomic analyses.
We generated iPSC lines from adult and juvenile HD onsets and age-related controls. We used these lines to obtain NPCs, MSNs, and organoids from HD patients and controls. Our models express markers such as Nestin and PAX6 in NPCs, MAP2 and DARPP32 in both MSNs and striatal organoids, as well as SOX2 and TBR1 in cortical organoids, confirming their specific fates. Moreover, we have detected morphological alterations in our HD models that correspond with neurodevelopmental abnormalities in HD previously reported in the literature.
Our iPSC lines have allowed us to generate in vitro models of HD that reproduce pathological features as they grow, potentially reinforcing the hypothesis of an impaired neurodevelopment in HD. Such changes should be further explored and targeted via neuromodulatory compounds, to assess the chances of reversing the obtained phenotypes into a physiological state.
Chairman: Raluca Contu
