Development of human brain organoids with functional vascular-like system
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA553561 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9661365.fastq.gz | Fastqsanger.gz | |||
| SRR9661366.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide an excellent platform to study human brain development and diseases in complex 3D tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to inner-most parts of hCOs. Previous studies demonstrated that the expression of human ETS variant 2 (hETV2) directly converts human fibroblasts to functional endothelial cells. Here, we engineered hESCs to ectopically express hETV2 to create in vitro vasculature in hCOs, namely vhCOs (vascularized hCOs). hETV2-expressing cells in hCOs contributed to forming a complex vascular network in hCOs. Importantly, the presence of vascularization resulted in enhanced functional maturation of organoids. We found that vhCOs acquired several blood-brain barrier (BBB) characteristics including increased expression of tight junctions, nutrient transporters, and trans-endothelial electrical resistance. Finally, hETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature that resemble early prenatal brain, and present a robust model to study brain disease in vitro.
2019-09-19 | GSE134049 | GEO
Project description:Generation of brain organoids for functional analysis
| PRJNA913949 | ENA
Project description:Vascular network-inspired diffusible scaffolds for engineering functional neural organoids
| PRJNA1157220 | ENA
Project description:Human brain organoids replicate much of the cellular diversity and developmental anatomy of the human brain. However, the physiology of neuronal circuits within organoids remains under-explored. With high-density CMOS microelectrode arrays and shank electrodes, we captured spontaneous extracellular activity from brain organoids derived from human induced pluripotent stem cells. We inferred functional connectivity from spike timing, revealing a large number of weak connections within a skeleton of significantly fewer strong connections. A benzodiazepine increased the uniformity of firing patterns and decreased the relative fraction of weakly connected edges. Our analysis of the local field potential demonstrate that brain organoids contain neuronal assemblies of sufficient size and functional connectivity to co-activate and generate field potentials from their collective transmembrane currents that phase-lock to spiking activity. These results point to the potential of brain organoids for the study of neuropsychiatric diseases, drug action, and the effects of external stimuli upon neuronal networks.
2022-07-15 | GSE207749 | GEO
Project description:Organoids, three-dimensional in vitro organ-like tissue cultures derived from stem cells, show promising potential for developmental biology, drug discovery, and regenerative medicine. However, the function and phenotype of current organoids, especially neural organoids, are still limited by insufficient diffusion of oxygen, nutrients, metabolites, signaling molecules, and drugs. Herein, we present Vascular network-Inspired Diffusible (VID) scaffolds to fully recapture the benefits of physiological diffusion physics for generating functional organoids and phenotyping their drug response. In a proof-of-concept application, the VID scaffolds, 3D-printed meshed tubular channel networks, support the successful generation of engineered human midbrain organoids almost without necrosis and hypoxia in commonly used well-plates. Compared to conventional organoids, these engineered organoids develop with more physiologically relevant features and functions including midbrain-specific identity, oxygen metabolism, neuronal maturation, and network activity. Moreover, these engineered organoids also better recapitulate pharmacological responses, such as neural activity changes to fentanyl exposure, compared to conventional organoids with significant diffusion limits. Combining these unique scaffolds and engineered organoids may provide insights for organoid development and therapeutic innovation.
2025-08-13 | GSE276401 | GEO
Project description:Vascular networks are critical for the development and maintenance of human tissues, as they support metabolism and regulate tissue growth and function. In vitro models such as organoids and organs-on-chip often have a limited capacity to recapitulate in vivo functional vascular networks and their integration within tissues. Most existing systems fail to mimic the structural and functional complexity of native capillary beds, lack physiological flow dynamics, and do not support vascular circulation. Here, we present a fully stem cell-derived microfluidic platform capable of generating perfusable vascular network organoids-on-chip with capillary-scale vessels, endothelial responses to biophysical forces, and physiologically accurate gene expression. Using this platform, we generate vascularized heart organoids-on-chip that replicate the dense capillary architecture of the heart and exhibit organ-specific vascular features and gene expression. These results establish a scalable and physiologically relevant approach for engineering and studying vascularized organoids under dynamic flow, with broad applications in developmental biology, disease modeling, and multi-organ in vitro systems.
2026-04-22 | GSE295488 | GEO
Project description:Brain vascular integrity is critical for brain health, and its disruption is implicated in many brain pathologies, including psychiatric disorders. Brain-vascular barriers are a complex cellular landscape composed of endothelial, glial, mural, and immune cells. Yet currently, little is known about these brain vascular-associated cells (BVACs) in health and disease. Previously, we have demonstrated that 14 days of chronic social defeat (CSD), a mouse paradigm that produces anxiety and depressive-like behaviors, causes cerebrovascular damage in the form of scattered microbleeds. Here, we developed a technique to isolate barrier-related cells from the mouse brain and subjected the cells to single-cell RNA sequencing. Using this isolation technique, we found an enrichment in BVAC populations, including distinct subsets of endothelial and microglial cells. In CSD compared to home-cage control, differential gene expression patterns disclosed biological pathways involving vascular dysfunction, vascular healing, and immune system activation. Overall, our work demonstrates a unique technique to study rare BVAC populations from fresh brain tissue and suggests that neurovascular dysfunction is a key driver of psychosocial stress-induced brain pathology.
2023-06-29 | GSE210577 | GEO
Project description:Brain organoids were generated from human iPS cells to evaluated the neuronal function of organoids derived neurons.
2024-12-31 | GSE221354 | GEO
Project description:Functional neuronal circuitry and oscillatory dynamics in human brain organoids
| PRJNA856997 | ENA
Project description:Blood vessels show various COVID-19-related conditions including thrombosis and cytokine propagation. Existing in vitro blood vessel models cannot represent the consequent changes in the vascular structure or determine the initial infection site, making it difficult to evaluate how epithelial and endothelial tissues are damaged. Here, we developed a microphysiological system (MPS) that co-culture the bronchial organoids and the vascular bed to analyze infection site and interactions. In this system, virus-infected organoids caused damage in vascular structure. However, vasculature was not damaged or infected when the virus was directly introduced to vascular bed. The knockout of interferon-related genes and inhibition of the JAK/STAT pathway reduced the vascular damage, indicating the protective effect of interferon response suppression. The results demonstrate selective infection of bronchial epithelial cells and vascular damage by cytokines and also indicate the applicability of MPS to investigate how the infection influences vascular structure and functions.
2024-01-11 | GSE216851 | GEO