3D Cerebral Organoids Research Articles

Maternal sevoflurane exposure induces temporary defects in interkinetic nuclear migration of radial glial progenitors in the fetal cerebral cortex through the Notch signalling pathway.

ObjectivesThe effects of general anaesthetics on fetal brain development remain elusive. Radial glial progenitors (RGPs) generate the majority of neurons in developing brains. Here, we evaluated the acute alterations in RGPs after maternal sevoflurane exposure.MethodsPregnant mice were exposed to 2.5% sevoflurane for 6 hours on gestational day 14.5. Interkinetic nuclear migration (INM) of RGPs in the ventricular zone (VZ) of the fetal brain was evaluated by thymidine analogues labelling. Cell fate of RGP progeny was determined by immunostaining using various neural markers. The Morris water maze (MWM) was used to assess the neurocognitive behaviours of the offspring. RNA sequencing (RNA‐Seq) was performed for the potential mechanism, and the potential mechanism validated by quantitative real‐time PCR (qPCR), Western blot and rescue experiments. Furthermore, INM was examined in human embryonic stem cell (hESC)‐derived 3D cerebral organoids.ResultsMaternal sevoflurane exposure induced temporary abnormities in INM, and disturbed the cell cycle progression of RGPs in both rodents and cerebral organoids without cell fate alternation. RNA‐Seq analysis, qPCR and Western blot showed that the Notch signalling pathway was a potential downstream target. Reactivation of Notch by Jag1 and NICD overexpression rescued the defects in INM. Young adult offspring showed no obvious cognitive impairments in MWM.ConclusionsMaternal sevoflurane exposure during neurogenic period temporarily induced abnormal INM of RGPs by targeting the Notch signalling pathway without inducing long‐term effects on RGP progeny cell fate or offspring cognitive behaviours. More importantly, the defects of INM in hESC‐derived cerebral organoids provide a novel insight into the effects of general anaesthesia on human brain development.

Revealing Tissue-Specific SARS-CoV-2 Infection and Host Responses using Human Stem Cell-Derived Lung and Cerebral Organoids.

SummaryCOVID-19 is a transmissible respiratory disease caused by a novel coronavirus, SARS-CoV-2, and has become a global health emergency. There is an urgent need for robust and practical in vitro model systems to investigate viral pathogenesis. Here, we generated human induced pluripotent stem cell (iPSC)-derived lung organoids (LORGs), cerebral organoids (CORGs), neural progenitor cells (NPCs), neurons, and astrocytes. LORGs containing epithelial cells, alveolar types 1 and 2, highly express ACE2 and TMPRSS2 and are permissive to SARS-CoV-2 infection. SARS-CoV-2 infection induces interferons, cytokines, and chemokines and activates critical inflammasome pathway genes. Spike protein inhibitor, EK1 peptide, and TMPRSS2 inhibitors (camostat/nafamostat) block viral entry in LORGs. Conversely, CORGs, NPCs, astrocytes, and neurons express low levels of ACE2 and TMPRSS2 and correspondingly are not highly permissive to SARS-CoV-2 infection. Infection in neuronal cells activates TLR3/7, OAS2, complement system, and apoptotic genes. These findings will aid in understanding COVID-19 pathogenesis and facilitate drug discovery.

PAUPAR and PAX6 sequentially regulate human embryonic stem cell cortical differentiation.

Long noncoding RNAs (lncRNAs) play a wide range of roles in the epigenetic regulation of crucial biological processes, but the functions of lncRNAs in cortical development are poorly understood. Using human embryonic stem cell (hESC)-based 2D neural differentiation approach and 3D cerebral organoid system, we identified that the lncRNA PAUPAR, which is adjacent to PAX6, plays essential roles in cortical differentiation by interacting with PAX6 to regulate the expression of a large number of neural genes. Mechanistic studies showed that PAUPAR confers PAX6 proper binding sites on the target neural genes by directly binding the genomic regions of these genes. Moreover, PAX6 recruits the histone methyltransferase NSD1 through its C-terminal PST enrichment domain, then regulate H3K36 methylation and the expression of target genes. Collectively, our data reveal that the PAUPAR/PAX6/NSD1 complex plays a critical role in the epigenetic regulation of hESC cortical differentiation and highlight the importance of PAUPAR as an intrinsic regulator of cortical differentiation.

Production of Phenotypically Uniform Human Cerebral Organoids from Pluripotent Stem Cells.

Recent advances in stem cell technology have allowed researchers to generate 3D cerebral organoids (COs) from human pluripotent stem cells (hPSCs). Indeed, COs have provided an unprecedented opportunity to model the developing human brain in a 3D context, and in turn, are suitable for addressing complex neurological questions by leveraging advancements in genetic engineering, high resolution microscopy, and tissue transcriptomics. However, the use of this model is limited by substantial variations in the overall morphology and cellular composition of organoids derived from the same pluripotent cell line. To address these limitations, we established a robust, high-efficiency protocol for the production of consistent COs by optimizing the initial phase of embryoid body (EB) formation and neural induction. Using this protocol, COs can be reproducibly generated with a uniform size, shape, and cellular composition across multiple batches. Furthermore, organoids that developed over extended periods of time (3-6 months) showed the establishment of relatively mature features, including electrophysiologically active neurons, and the emergence of oligodendrocyte progenitors. Thus, this platform provides a robust experimental model that can be used to study human brain development and associated disorders. Graphic abstract: Overview of cerebral organoid development from pluripotent stem cells.

Enhanced Neuronal Activity and Asynchronous Calcium Transients Revealed in a 3D Organoid Model of Alzheimer’s Disease

Advances in the development of three-dimensional (3D) brain organoids maintained in vitro have provided excellent opportunities to study brain development and neurodegenerative disorders, including Alzheimer's disease (AD). However, there remains a need to generate AD organoids bearing patient-specific genomic backgrounds that can functionally recapitulate the key features observed in the AD patient's brain. To address this need, we described a strategy to generate self-organizing 3D cerebral organoids which develop a functional neuronal network connectivity. This was achieved by neuroectoderm induction of human pluripotent stem cell (hPSCs) aggregates and subsequent differentiation into desired neuroepithelia and mature neurons in a 3D Matrigel matrix. Using this approach, we successfully generated AD cerebral organoids from human pluripotent stem cells (hPSCs) derived from a familial AD patient with a common mutation in presenilin 2 (PSEN2N141I). An isogenic control with an identical genetic background but wild-type PSEN2 was generated using CRISPR/Cas9 technology. Both control and AD organoids were characterized by analyzing their morphology, the Aβ42/Aβ40 ratio, functional neuronal network activity, drug sensitivity, and the extent of neural apoptosis. The spontaneous activity of the network and its synchronization was measured in the organoids via calcium imaging. We found that compared with the mutation-corrected control organoids, AD organoids had a higher Aβ42/Aβ40 ratio, asynchronous calcium transients, and enhanced neuronal hyperactivity, successfully recapitulating an AD-like pathology at the molecular, cellular, and network level in a human genetic context. Moreover, two drugs which increase neuronal activity, 4-aminopyridine (4-AP) and bicuculline methochloride, induced high-frequency synchronized network bursting to a similar extent in both organoids. Therefore, our study presents a promising organoid-based biosystem for the study of the pathophysiology of AD and a platform for AD drug development.

IPSC‐derived engineered cerebral organoids (enCORs) as in vitro models of tauopathy

AbstractBackgroundFamilial Alzheimer’s disease (fAD) is caused by mutations in PSEN1, PSEN2 and APP. PSEN1 forms the catalytic core of g‐secretase, a membrane protease which cleaves numerous substrates including APP and Notch. We have previously shown that our panel of fAD patient‐derived iPSCs show altered APP processing and Ab generation. Here we investigated whether mutations led to altered Notch cleavage in neural precursors. We hypothesised that reduced Notch cleavage in fAD lines would promote premature differentiation during iPSC neuronal differentiation and during adult hippocampal neurogenesis.MethodWe generated 2D cortical neurons and 3D cerebral organoids from a panel of 14 donor‐derived iPSC lines (5 controls, 2 APP mutation lines and 7 PSEN1 mutation lines). Neurogenesis was quantified via the proportion of neural precursors versus the number of post‐mitotic neurons at timepoints of neural commitment. In addition, we quantified newly generated neurons in the post‐mortem hippocampus of 3 control brains and 7 brains derived from fAD mutation carriers.ResultWe describe a small, yet reproducible premature differentiation phenotype in lines containing mutations in PSEN1 during in vitro neurogenesis. This is, at least in part, due to reduced Notch signalling; which drives terminal differentiation. These findings are corroborated in independent orthogonal iPSC systems, namely 2D neurogenesis and 3D organoid differentiation. We see describe robust, quantifiable neurogenesis in post‐mortem tissue using b‐III‐tubulin immunohistochemistry. Results are suggestive of mutation‐specific effects and also a premature ageing phenotype in fAD tissue.ConclusionThese findings reveal insights into the functional outcomes of fAD mutations. Mutations in PSEN1, but not APP, alter Notch signalling in neural precursors, which in turn drives premature terminal differentiation. Premature differentiation and mutation‐specific differences both necessitate careful consideration for drug design and patient stratification.

Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures.

Inflammatory processes in the brain are orchestrated by microglia and astrocytes in response to activators such as pathogen-associated molecular patterns, danger-associated molecular patterns and some nanostructures. Microglia are the primary immune responders in the brain and initiate responses amplified by astrocytes through intercellular signaling. Intercellular communication between neural cells can be studied in cerebral organoids, co-cultures or in vivo. We used human cerebral organoids and glioblastoma co-cultures to study glia modulation by dendritic polyglycerol sulfate (dPGS). dPGS is an extensively studied nanostructure with inherent anti-inflammatory properties. Under inflammatory conditions, lipocalin-2 levels in astrocytes are markedly increased and indirectly enhanced by soluble factors released from hyperactive microglia. dPGS is an effective anti-inflammatory modulator of these markers. Our results show that dPGS can enter neural cells in cerebral organoids and glial cells in monocultures in a time-dependent manner. dPGS markedly reduces lipocalin-2 abundance in the neural cells. Glioblastoma tumoroids of astrocytic origin respond to activated microglia with enhanced invasiveness, whereas conditioned media from dPGS-treated microglia reduce tumoroid invasiveness. Considering that many nanostructures have only been tested in cancer cells and rodent models, experiments in human 3D cerebral organoids and co-cultures are complementary in vitro models to evaluate nanotherapeutics in the pre-clinical setting. Thoroughly characterized organoids and standardized procedures for their preparation are prerequisites to gain information of translational value in nanomedicine. This study provides data for a well-characterized dendrimer (dPGS) that modulates the activation state of human microglia implicated in brain tumor invasiveness.

Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes.

Neonatal herpes simplex virus type 1 (HSV-1) infections contribute to various neurodevelopmental disabilities and the subsequent long-term neurological sequelae into the adulthood. However, further understanding of fetal brain development and the potential neuropathological effects of the HSV-1 infection are hampered by the limitations of existing neurodevelopmental models due to the dramatic differences between humans and other mammalians. Here we generated in vitro neurodevelopmental disorder models including human induced pluripotent stem cell (hiPSC)-based monolayer neuronal differentiation, three-dimensional (3D) neuroepithelial bud, and 3D cerebral organoid to study fetal brain development and the potential neuropathological effects induced by the HSV-1 infections. Our results revealed that the HSV-1-infected neural stem cells (NSCs) exhibited impaired neural differentiation. HSV-1 infection led to dysregulated neurogenesis in the fetal neurodevelopment. The HSV-1-infected brain organoids modelled the pathological features of the neurodevelopmental disorders in the human fetal brain, including the impaired neuronal differentiation, and the dysregulated cortical layer and brain regionalization. Furthermore, the 3D cerebral organoid model showed that HSV-1 infection promoted the abnormal microglial activation, accompanied by the induction of inflammatory factors, such as TNF-α, IL-6, IL-10, and IL-4. Overall, our in vitro neurodevelopmental disorder models reconstituted the neuropathological features associated with HSV-1 infection in human fetal brain development, providing the causal relationships that link HSV biology with the neurodevelopmental disorder pathogen hypothesis.

Neuronal defects in a human cellular model of 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric disease. Here we generated induced pluripotent stem cells from 15 individuals with 22q11DS and 15 control individuals and differentiated them into three-dimensional (3D) cerebral cortical organoids. Transcriptional profiling across 100 days showed high reliability of differentiation and revealed changes in neuronal excitability-related genes. Using electrophysiology and live imaging, we identified defects in spontaneous neuronal activity and calcium signaling in both organoid- and 2D-derived cortical neurons. The calcium deficit was related to resting membrane potential changes that led to abnormal inactivation of voltage-gated calcium channels. Heterozygous loss of DGCR8 recapitulated the excitability and calcium phenotypes and its overexpression rescued these defects. Moreover, the 22q11DS calcium abnormality could also be restored by application of antipsychotics. Taken together, our study illustrates how stem cell derived models can be used to uncover and rescue cellular phenotypes associated with genetic forms of neuropsychiatric disease.

Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids

Acrylamide (ACR) is a common food contaminant with neurotoxic effects that are formed in the Maillard browning reaction during the heat processing of food. Importantly, pregnant women are also exposed to ACR in food during pregnancy and thus, the fetus is likely affected. However, the mechanisms of ACR-caused neurotoxicity on human brain development are still unclear. Many recent studies employed cerebral organoids based on human embryonic stem cells (hESC) for investigating human neurodevelopmental disorders and toxicity. Here, we generated hESC-derived cerebral organoids to evaluate the neurodevelopmental toxicity of ACR. The results indicated that exposure to ACR significantly altered the transcriptional profile, increased nuclear factor erythroid 2-related factor 2 (NRF2)-mediated gene expression, induced cell apoptosis, repressed neuronal differentiation, and promoted tau hyperphosphorylation in cerebral organoids, which may contribute to ACR-induced neurodevelopmental toxicity. These results indicate that the risk of transplacental exposure of the fetus to ACR should be evaluated and pregnant mothers should limit their exposure to ACR.

Rapid induction of gliogenesis in OLIG2 and NKX2.2-expressing progenitors-derived spheroids.

Glial cells are crucial for the development of the central nervous system and the maintenance of chemical homeostasis. The process of gliogenesis has been well studied in the rodent brain, but it remains less well studied in the human brain. In addition, rodent glial cells differ from human counterparts in terms of morphologies, functions, and anatomical locations. Cerebral organoids (also referred to as spheroids) derived from human pluripotent stem cells (hPSCs) have been developed and are suitable cell‐based models for researching developmental and neurodegenerative diseases. The in vitro generation of glia, including astrocytes and oligodendrocytes, from such organoids represents a promising tool to model neuronal diseases. Here, we showed that three‐dimensional (3D) culture of OLIG2‐ and NKX2.2‐expressing neurospheres produced efficiently mature astrocytes and oligodendrocytes in terms of morphologies and expression pattern recapitulating native 3D environment. Our findings provide important insights for developmental research of the human brain and glial specification that may facilitate patient‐specific disease modeling.

NitroSynapsin ameliorates hypersynchronous neural network activity in Alzheimer hiPSC models.

Beginning at early stages, human Alzheimer’s disease (AD) brains manifest hyperexcitability, contributing to subsequent extensive synapse loss, which has been linked to cognitive dysfunction. No current therapy for AD is disease-modifying. Part of the problem with AD drug discovery is that transgenic mouse models have been poor predictors of potential human treatment. While it is undoubtedly important to test drugs in these animal models, additional evidence for drug efficacy in a human context might improve our chances of success. Accordingly, in order to test drugs in a human context, we have developed a platform of physiological assays using patch-clamp electrophysiology, calcium imaging, and multielectrode array (MEA) experiments on human (h)iPSC-derived 2D cortical neuronal cultures and 3D cerebral organoids. We compare hiPSCs bearing familial AD mutations vs. their wild-type (WT) isogenic controls in order to characterize the aberrant electrical activity in such a human context. Here, we show that these AD neuronal cultures and organoids manifest increased spontaneous action potentials, slow oscillatory events (~1 Hz), and hypersynchronous network activity. Importantly, the dual-allosteric NMDAR antagonist NitroSynapsin, but not the FDA-approved drug memantine, abrogated this hyperactivity. We propose a novel model of synaptic plasticity in which aberrant neural networks are rebalanced by NitroSynapsin. We propose that hiPSC models may be useful for screening drugs to treat hyperexcitability and related synaptic damage in AD.

Isolation and Culture of Human-Induced Pluripotent Stem Cell-Derived Cerebral Organoid Cells.

The advent of human-induced pluripotent stem cell (iPSC)-derived three-dimensional (3D) cerebral organoids provides unprecedented opportunities of modeling human brains in states of health and disorder. Emerging data supports that cerebral organoids allow for more relevant in vitro systems for studying the human brain system and diseases than the current widely used 2D monolayer cell culture. Thus, the ability to isolate, culture, and maintain human brain cells from cerebral organoids is highly needed, particularly for studies on organoid-derived cell-type-specific signaling and their electrophysiological properties. Here we present a protocol to isolate and culture brain cells from 2-month human iPSC-derived cerebral organoids. The dissociation and plating of cells from organoids takes 3-4h. The dissociated cells can be maintained in culture for up to at least 3weeks. Some cells expressed the neuron-specific marker microtubule-associated protein 2 and exhibited spontaneous action potentials.

Challenges and future perspectives for 3D cerebral organoids as a model for complex brain disorders

The human brain is made up of billions of neurons and glial cells which are interconnected and organized into specific patterns of neural circuitry, and hence is arguably the most sophisticated organ in human, both structurally and functionally. Studying the underlying mechanisms responsible for neurological or neurodegenerative disorders and the developmental basis of complex brain diseases such as autism, schizophrenia, bipolar disorder, Alzheimer’s and Parkinson’s disease has proven challenging due to practical and ethical limitations on experiments with human material and the limitations of existing biological/animal models. Recently, cerebral organoids have been proposed as a promising and revolutionary model for understanding complex brain disorders and preclinical drug screening.

M89 - MODELING HUMAN CORTICAL BRAIN DEVELOPMENT BY THE GENERATION OF CEREBRAL ORGANOIDS FROM PATIENT-SPECIFIC STEM CELLS FOR THE ANALYSIS OF SCHIZOPHRENIA GENETICS

Background Characteristics of schizophrenia include the deregulation of the glutamatergic and the GABAergic neurotransmission and the degeneration of predominantly inhibitory interneurons within the cortex of the human brain. Cortical development was extensively studied in rodents, but the unique and complex architecture of the human cortex differs dramatically from brain of established animal models. Accordingly, the analysis of schizophrenia animal models is limited by the species differences, which requires the development of adequate human in vitro models mimicking the human cortical brain development. Schizophrenia is associated with DNA variations suggesting that genetic factors contribute to onset, progression and treatment of the disease. We generated induced pluripotent stem cells (iPS cells), which allow the generation of disease- and patient-specific neuronal cultures for the analysis of genetic factors. However, the functional characterization of genetic factors requires the analysis of advanced tissue-based 3D disease models. Therefore, we generated cerebral organoids for mimicking aspects of the human cortical development. Methods Human iPS cells from healthy donors and patient-specific iPS cells from schizophrenia patients were differentiated into permanent Neural Stem Cells (NSCs). Transcript and protein analysis confirmed the differentiation status of iPS cells and NSCs. NSCs were characterized in cellular 2D differentiation models. NSCs were further differentiated as free-floating neurospheres to acquire functional 3D organoids. Cells were analyzed by transcript and protein analysis. Cryosectioning of organoids was applied to visualize the distribution of different neuronal subtypes. Results Protein and transcript analysis of specific markers including OCT4 and the activity of alkaline phosphatases verified pluripotency in patient-derived iPS cells. The analysis of several NSC markers such as SOX2 and PAX6 indicated stable generation of permanent NSCs from patient-specific iPS cells. Patient-specific iPS cells were successfully differentiated into progenitor cells expressing a variety of neural lineage markers including neural makers such as TUBB3 and STX as wells as glia cell markers such as GFAP and O4. Immunostaining and whole-cell patch-clamp recordings of mature neurons showed the presence of different neuronal subtypes including inhibitory GABAergic neurons. NSCs were also successfully applied to the generation of 3D cerebral organoids. The 3D organoid differentiation model showed the RNA and protein expression of neural lineage markers similar to cells obtained from the 2D monolayer cultures. The expression pattern of cortical markers such as TBR1 observed in cryosections of organoids revealed the induction of cortical layers mimicking the developing human cortex. Discussion We successfully generated 3D cerebral organoids mimicking aspects of the early human brain development. These culture systems enable functional studies of healthy and diseased human cortical development for the analysis of neurodevelopmental diseases including schizophrenia.

The Mechanical Mechanism of Cortical Folding on 3D Cerebral Organoids

The Mechanical Mechanism of Cortical Folding on 3D Cerebral Organoids

93. Modeling Human Brain Development and Developmental Diseases Using HiPSCs

Three dimensional (3D) cerebral organoid cultures from human iPSCs have been recently developed to recapitulate the cytoarchitecture of the developing brain. This system offers unique advantages in understanding molecular and cellular mechanisms governing embryonic neural development and in modeling congenital neurodevelopmental disorders, such as microcephaly. We have improved the organoid technology and developed a protocol to produce forebrain-specific organoids derived from human iPSCs using a novel miniaturized spinning bioreactor that recapitulate the human embryonic cortical development. ZIKV, a mosquito-borne flavivirus, has re-emerged as a major public health concern globally because ZIKV causes congenital defects, including microcephaly, and is also associated with Guillain-Barré syndrome in infected adults. We found that ZIKV exhibit specific tropism towards human neural progenitor cells and results in cell death and defects in neural development. I will discuss our recent work in further dissecting the molecular mechanisms underlying the ZIKV pathogenesis and microcephaly.

Proof‐of‐Concept in a 3D Culture Model of Glioma Invasion: Towards Personalized Therapeutics in Brain Cancer

Glioma is a highly aggressive form of brain cancer, with some subtypes having 5‐year survival rates of less than 5%. Tumor cell invasion into the surrounding parenchyma seems to be the primary driver of these poor outcomes, as most gliomas recur within 2 cm of the original surgically‐resected tumor. Many current approaches to the development of anticancer therapy attempt to target genetic weaknesses in a particular cancer, but may not take into account the microenvironment experienced by a tumor and patient‐specific genetic differences in susceptibility to treatment.The primary aim of our research program is to overcome these limitations by ultimately developing 3D cerebral organoids generated from patient‐derived induced pluripotent stem cells (iPSCs), in which we will screen to identify an optimal treatment regimen by combining the organoids with patient‐derived tumor cells. As a proof‐of‐concept of this approach, we developed a system in which we could model the invasion of human glioma cells into mouse neural progenitor cell‐derived spheroids. Here we demonstrate the utility of such an approach, and find that we can follow invasion of human tumor cells using cell tracking dyes and 3D laser scanning confocal microscopy, both in real time and in fixed samples. These results were validated using conventional cryosectioning. We go on to show broad applicability of this system by using two different tumor cell lines, and two different mouse genetic backgrounds, attempting to mimic differences that might be observed in tumor and patient brain tissue, respectively. Having obtained this proof‐of‐concept, we will next recapitulate these results in a fully humanized system using spheroids and then cerebral organoids from human iPSCs, before moving on to patient‐derived cultures. This stepwise approach could ultimately lead to truly personalized treatments for brain cancer.Support or Funding InformationDvP is supported by the UBC Faculty of Medicine, the UBC Summer Student Research Program, and the Mach‐Gaensslen Foundation. CCN is supported by the Canada Research Chair program and a grant from the Canadian Cancer Society. WCS is supported by the Canadian Cancer Society.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Fused cerebral organoids model interactions between brain regions.

Human brain development involves complex interactions between different areas, including long distance neuronal migration or formation of major axonal tracts. 3D cerebral organoids allow the growth of diverse brain regions in vitro, but the random arrangement of regional identities limits the reliable analysis of complex phenotypes. Here, we describe a co-culture method combining various brain regions of choice within one organoid tissue. By fusing organoids specified toward dorsal and ventral forebrain, we generate a dorsal-ventral axis. Using fluorescent reporters, we demonstrate robust directional GABAergic interneuron migration from ventral into dorsal forebrain. We describe methodology for time-lapse imaging of human interneuron migration that is inhibited by the CXCR4 antagonist AMD3100. Our results demonstrate that cerebral organoid fusion cultures can model complex interactions between different brain regions. Combined with reprogramming technology, fusions offer the possibility to analyze complex neurodevelopmental defects using cells from neurological disease patients, and to test potential therapeutic compounds.

P.1.c.014 - The analysis of neurodevelopmental disorders by the generation of 3D cerebral organoids mimicking the human cerebral development

P.1.c.014 - The analysis of neurodevelopmental disorders by the generation of 3D cerebral organoids mimicking the human cerebral development