From 22 – 25 October 2025, the EMBO | EMBL Symposium ‘Organoids’ highlighted how 3D stem cell–derived organoids have transformed the study of tissue biology, particularly in human systems. The meeting welcomed 440 participants on site and 179 online, reflecting the strong interest in this rapidly advancing field.

With their high fidelity in modelling real tissues, organoids now play a central role in research on development, homeostasis, regeneration, and disease, as well as in drug discovery and regenerative medicine. The fifth edition of this established meeting brought together researchers from multiple disciplines to discuss how organoids can be formed and maintained, how they can be applied to study disease, and how they might one day be used to regenerate or replace human tissues. A key focus of the 2025 programme was the integration of complementary technologies such as multiomics, engineered embryo models, and bioengineering, alongside a stronger emphasis on cancer research.

Along the helices of the Advanced Training Centre, 215 posters were presented, offering a broad snapshot of current research. From these, five poster prize winners were selected, and we are pleased to introduce them and their work in this post.

Profiling human choroid plexus organoid maturation and response to acute mechanical injury

Presenter: Elizabeth Apsley

Authors: Elizabeth Apsley, Ivan Imaz Rosshandler, Marian Fernandez Otero, See Swee Tang, Madeline Lancaster, Laura Pellegrini

Abstract:

The choroid plexus (ChP) is an important brain structure which protects and regulates the brain environment. The ChP is responsible for secreting cerebrospinal fluid (CSF), a vital source of nutrients and signalling molecules that maintain brain homeostasis. By forming a tightly regulated barrier, the ChP also protects the brain from pathogens and toxins. In addition, the ChP acts as a neuroimmune interface, coordinating immune signalling and forming a gateway for peripheral immune cell entry. Human stem cell derived ChP organoids have been shown to accurately model ChP functions such as active secretion of CSF and selective permeability to small molecules, and have been used to study pathogen entry to the brain. Our work continues to expand the characterisation of this novel organoid model in relation to human in vivo ChP development. We profiled ChP organoids using scRNAseq across the differentiation time course to map the developmental trajectory of the cell types present. Focusing on the epithelial lineage we identified dynamic changes in gene expression across maturation from cortical hem to mature secretory ChP epithelium. As in vivo, we found that in the organoid model ChP epithelium stops proliferating around day 70, and expresses markers of mature tissue at later timepoints. We also observed changes in cilia clustering and length during epithelial maturation reflecting post mitotic features observed in vivo. Next, we used the organoid model to investigate the response of the ChP epithelial cells to mechanical injury. Following physical damage, we found that the ChP secretes cytokines and chemokines. We also discovered increased signatures of fibroblasts and tissue remodelling which contribute to repair. In conclusion, ChP organoids are a powerful tool for studying the human ChP and associated diseases throughout life from development to adult. Moreover, they provide an accessible human model to probe mechanisms of acute injury and repair.

Due to the confidentiality of the unpublished data, we cannot share the poster.

Poster prize kindly sponsored by EMBO reports

Organoid-on-a-chip for dissecting age- and cytokine-driven neurovascular dysfunction

Presenter: Paris Brown

Authors: Paris Brown, Shyni Varghese, Surjendu Maity

Abstract:

Persistent neuroinflammation is a crucial factor in the progression of neurodegenerative diseases. However, few human relevant platforms are available to study the various drivers of this process. We describe two complementary organoid on a chip systems that model different aspects of this phenomenon: one focuses on neuroinflammation caused by peripheral inflammatory stress, and the other examines metabolic brain aging, both using human derived neural components.
The neurovascular unit (NVU) device comprises a perfusable endothelial lumen, astrocytes, pericytes, microglia, and a neurospheroid. When exposed to IL 1β, it causes disruption of the blood brain barrier, indicated by the loss of ZO 1 and increased transport of FITC dextran. This exposure also induces glial activation and hampers neuronal firing. These responses highlight important aspects of neurovascular dysfunction caused by inflammation.
Brain aging was modeled using FK866 to deplete NAD⁺in 3D neurospheroids and microglia. This causes key aging features, including DNA damage, mitochondrial dysfunction, microglial priming, and reduced synaptic function. Functional analyses showed decreased calcium signaling and spike activity, even without added pro inflammatory cytokines.
These platforms offer a versatile tool for mechanistic studies on how peripheral and intrinsic stressors affect the brain. Moving forward, we will incorporate aged brain organoids into the NVU on a chip to explore the effects of an aging brain on vascular integrity, shifting our focus from one way interactions to a more comprehensive examination of the bidirectional relationship between the brain and blood vessels.

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Developing complex human liver organoids to investigate the cellular crosstalk between the epithelia and stromal niche

Presenter: Sagarika Dawka

Authors: Sagarika Dawka, Lei Yuan, Meritxell Huch, Anke Liebert, Robert Arnes, Fabian Rost, Yohan Kim

Abstract:

The mammalian liver is a highly complex organ, responsible for crucial functions including drug detoxification, metabolic regulation, and bile drainage. It has a unique tissue architecture consisting of functional units called lobules and is composed of multiple cell types, such as epithelial and stromal cells, for optimal function. The development of patient derived organoid models has enabled the study of this complex organ in vitro, in healthy as well as diseased states. However, they require further improvements, especially in terms of differentiation and architecture fidelity, to gain a closer representation of the native tissue. Additionally, the current patient derived liver organoid models lack representation of the non parenchymal cell types, critical for homeostasis in vivo. This project aims to overcome these limitations by developing an enhanced liver organoid model that can recapitulate both the architecture and the heterogeneous cell populations present in the mammalian liver. This would enable the examination of cell cell interactions among epithelial and stromal cells, and would improve our understanding of their significance in liver health and disease.

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Poster prize kindly sponsored by The EMBO Journal

SMN deficiency disrupts lineage specification in neuromesodermal progenitors revealed by a human neuromuscular organoid model of SMA

Presenter: Zeynep Dokuzluoglu

Authors: Zeynep Dokuzluoglu, Kartik Jatwani, Tobias Grass, Antonio Caldarelli, Natalia Rodriguez Muela

Abstract:

Whether neurodevelopmental defects contribute to selective neuronal vulnerability in neurodegenerative diseases (NDs) is an emerging and intriguing question. We addressed this in the context of Spinal Muscular Atrophy (SMA), an early onset ND affecting spinal motor neurons (MNs) SMA is caused by the deficiency of Survival of Motor Neuron (SMN) protein, which is critical for RNA splicing and highly expressed during neural development. We thus hypothesized that SMN deficiency alters development and renders MNs vulnerable to stress.

To test this, we established a guided ventral neuromuscular organoid (vNMO) protocol from neuromesodermal progenitors (NMPs) and applied it to a cohort of hiPSC lines, including two healthy controls, two SMA type 1 (severe form) patient derived lines, and their isogenic controls in which SMN levels were restored via CRISPR Cas9 editing. This 3D system enabled modeling of spinal cord and neuromuscular development with lineage fidelity.

scRNA seq revealed a mesodermal fate bias in early SMA vNMOs compared to the healthy vNMOs and rescued in isogenic controls. This phenotype was mirrored in E10.5 SMA mouse embryos, which showed reduced neural tube area and increased mesodermal tissue compared to healthy littermates. In later stage vNMOs, this skewed lineage allocation resulted in reduced MN output, potentially impairing neuromuscular junction formation. Mechanistically, SMA NMPs showed decreased SOX2 and upregulated canonical WNT signaling, two key regulators of NMP fate. WNT inhibition reversed the SMA vNMOs mesodermal bias. We further identified an SMN dependent isoform switch in a known SOX2 regulator in both hiPSCs and vNMOs; and, importantly, its knockdown rescued neural lineage commitment in SMA vNMOs.

Our data reveal a novel developmental role for SMN in NMP lineage specification and demonstrate how organoid models can uncover early cellular mis specifications underlying neuromuscular diseases. This approach provides both mechanistic insight and therapeutic entry points for SMA and other neurodevelopmentally rooted disorders.

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Poster prize kindly sponsored by FEBS Letters

Time-resolved scRNA-seq identifies limits in colonic epithelial de-differentiation

Presenter: Nithyapriya Kumar

Authors: Nithyapriya Kumar, Ieva Norvaisaite, Lars Custers, Alexandra Vogel, David Keller, Helmuth Gehart

Abstract:

Upon injury or stem cell ablation, the regeneration of intestinal epithelium is facilitated by de differentiation of differentiated cells. Multiple studies have shown that almost all intestinal differentiated cell types can de differentiate; however, whether only early differentiation stages contribute to the process or whether plasticity is maintained during all states of maturity remains unknown. Furthermore, the mechanisms that underlie and orchestrate the de differentiation process remain unexplored. First, we investigated whether all differentiated cells retained de differentiation potential. Using time resolved scRNA seq, we observed that Bmp2 induced differentiation of organoids resulted in a diverse population of mature colonocytes. Upon reseeding in a de differentiation promoting environment, Clca4a+ colonocytes failed to de differentiate and retained a fully differentiated state. In contrast, colonocytes at earlier stages of differentiation (prior to Clca4a expression) were able to reacquire stem cell function. This finding suggested the existence of a plasticity limit in the absorptive lineage. Therefore, we investigated how systematic perturbation of signaling cascades modulated de differentiation outcomes. Using an image based high throughput organoid screening assay, we identified protein kinase C alpha (PRKCA), a calcium activated protein kinase predominantly expressed in de differentiating cells, as a critical inhibitor of outgrowth of organoids from fully mature colonocytes. Additionally, we found that c Met, a hepatocyte growth factor receptor, suppressed the stemness potential of cells that had undergone de differentiation. Combined PRKCA and c Met inhibition, therefore, has the potential to enhance the de differentiation capacity of fully mature cells and shift the limits of plasticity. In summary, our findings shed light on the mechanisms and signalling pathways underlying the process of de differentiation.

Due to the confidentiality of the unpublished data, we cannot publish the poster.

The EMBO | EMBL Symposium ‘Organoids: modelling organ development and disease in 3D‘ took place from 22 – 25 October 2025 at EMBL Heidelberg and virtually.