Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection [RNA-seq]

ABSTRACT: The human cerebral cortex possess distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotency stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain. Here, we report optimized organoid culture methods that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo. Neurons within the organoids are functional and exhibit network-like activities. We further demonstrate the utility of the organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying new candidate receptors and therapeutic compounds that can mitigate its desructive actions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97919 | GEO | 2017/10/11

SECONDARY ACCESSION(S): PRJNA383338

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection [expression array]

Project description:The human cerebral cortex possess distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotency stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain. Here, we report optimized organoid culture methods that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo. Neurons within the organoids are functional and exhibit network-like activities. We further demonstrate the utility of the organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying new candidate receptors and therapeutic compounds that can mitigate its desructive actions.

2017-10-11 | GSE97872 | GEO

Combination of a microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Project description:Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix (BEM) to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with BEM significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.

2021-06-02 | PXD025397 | Pride

Human brain organoids assemble functionally integrated bilateral optic vesicles

Project description:During embryogenesis, optic vesicles develop from the diencephalon via a complex process of organogenesis. Using iPSC-derived human brain organoids, we attempted to simplify the complexities and demonstrate the formation of forebrain-associated bilateral optic vesicles, cellular diversity, and functionality. Around day thirty, brain organoids could assemble optic vesicles, which progressively develop as visible structures within sixty days. These optic vesicle-containing brain organoids (OVB-Organoids) constitute a developing optic vesicle’s cellular components, including the primitive cornea and lens-like cells, developing photoreceptors, retinal pigment epithelia, axon-like projections, and electrically active neuronal networks. Besides, OVB-Organoids also display synapsin-1, CTIP-positive, myelinated cortical neurons, and microglia. Interestingly, various light intensities could trigger photoreceptor activity of OVB-Organoids, and light sensitivities could be reset after a transient photo bleach blinding. Thus, brain organoids have the intrinsic ability to self-organize forebrain-associated primitive sensory structures in a topographically restricted manner and can allow conducting interorgan interaction studies within a single organoid.

2021-07-08 | GSE179438 | GEO

Silk scaffolding drives self-assembly of functional and mature human brain organoids [scRNA-seq]

Project description:Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional (3D) structures provide a unique opportunity to generate cytoarchitecture and cell-cell interactions reminiscent of human brain complexity in a dish. However, current in vitro brain organoid methodologies often result in intra-organoid variability, limiting their use in recapitulating later developmental stages as well as in disease modeling and drug discovery. In addition, cell stress and hypoxia resulting from long-term culture lead to incomplete maturation and cell death within the inner core. Here, we used a recombinant silk microfiber network as a scaffold to drive human PSCs to self-arrange into engineered cerebral organoids. Silk scaffolding promoted neuroectoderm formation and reduced heterogeneity of cellular organization within individual organoids. Bulk and single cell transcriptomics confirmed that silk cerebral organoids display more homogeneous and functionally mature neuronal properties than organoids grown in the absence of silk fibers. Furthermore, oxygen sensing analysis showed that silk scaffolds create more favorable growth and differentiation conditions by facilitating the delivery of oxygen and nutrients. Silk-engineering platform appears to reduce intra-organoid variability and enhances functional maturation during spontaneous self-patterning in human brain organoid differentiation.

2022-02-12 | GSE196423 | GEO

Silk scaffolding drives self-assembly of functional and mature human brain organoids [RNA-seq]

2022-05-17 | GSE202992 | GEO

Self-organized yolk sac-like organoids allow for scalable generation of multipotent hematopoietic progenitor cells from human induced pluripotent stem cells

Project description:The human definitive yolk sac is an important organ supporting the early developing embryo through nutrient supply and by facilitating the establishment of the embryonic circulatory system. However, the molecular and cellular biology of the human yolk sac remains largely obscure due to the lack of suitable in vitro models. Here, we show that human induced pluripotent stem cells (hiPSCs) co-cultured with various types of stromal cells as spheroids self-organize into yolk sac-like organoids without the addition of exogenous factors. Yolk sac-like organoids recapitulated a yolk sac specific cellular complement and structures as well as the functional ability to generate definitive hematopoietic progenitor cells (HPCs). Furthermore, sequential hemato-vascular ontogenesis could be observed during organoid formation. Notably, our organoid system can be performed in a scalable, autologous, and xeno-free condition, thereby providing an important model of human definitive yolk sac development and allows for efficient bulk generation of hiPSC-derived HPCs.

2021-05-05 | GSE157140 | GEO

Rapamycin mitigates Valproic Acid-induced teratogenicity in human and animal models by suppressing AP-1-mediated senescence

Project description:Valproic acid (VPA) is an effective and widely used anti-seizure medication but is teratogenic when used during pregnancy, affecting brain and spinal cord development for reasons that remain largely unclear. Here we designed a genetic recombinase-based SOX10 reporter system in human pluripotent stem cells that enables tracking and lineage tracing of Neural Crest cells (NCCs) in a human organoid model of the developing neural tube. We found that VPA induces extensive cellular senescence and promotes mesenchymal differentiation of human NCCs at the expense of neural lineages. We next show that the clinically-approved drug, Rapamycin, inhibits AP1-mediated senescence and restores aberrant NCC differentiation trajectory in human organoids exposed to VPA. Notably, in vivo validation in developing zebrafish highlighted the therapeutic promise of this approach. Collectively our data identifies a novel mechanism for VPA-associated neurodevelopmental teratogenicity and a potential pharmacological preventative strategy. The results exemplify the power of genetically modified human stem cell-derived organoid models for drug discovery and safety testing.

2023-09-05 | GSE241903 | GEO

RNA-seq of brain organoids from human NKX2.1(GFP/w) hESCs treated with patterning molecules

Project description:There are on-going efforts to steer brain organoid development toward distinct regional identities by supplying cues in defined culture conditions. Here we incubated developing organoids with a number of patterning molecules at different concentrations to assess their effects on establishing brain region identities.

2021-02-11 | E-MTAB-10037 | biostudies-arrayexpress

Trans-omic Profiling Uncovers Molecular Controls of the Early Human Cerebral Organoid Formation

Project description:Defining molecular controls that orchestrate human brain development is essential for uncovering the complexity behind neurodevelopment and the pathogenesis of neurological disorders. Due to the difficulties in accessing embryonic and fetal brain tissues, the differentiation of human pluripotent stem cell (hPSC)-derived three-dimensional neural organoids has made it possible to recapitulate this developmental process in vitro and provide a unique opportunity to investigate human brain development and disease. To elucidate the molecular programs that drive this highly dynamic process, here, we generate a comprehensive trans-omic map of the phosphoproteome, proteome, and transcriptome of the initial stages of pluripotency and neural differentiation towards the formation of cerebral organoids. Our integrative analysis uncovers key phospho-signalling events underlying neural lineage differentiation, and their convergence on transcriptional (co-)factors and chromatin remodellers that govern downstream gene regulatory networks (GRNs). Comparative analysis with developing human and mouse embryos using these GRNs demonstrates the fidelity of our early cerebral organoids in modelling embryonic brain development. Finally, we demonstrate biochemical modulation of the AKT signalling as a key molecular switch for controlling human cerebral organoid formation. Our data provides a comprehensive resource to gain insight into the molecular controls in human embryonic brain development and also provide a guide for future development of protocols for human cerebral organoid differentiation.

2024-04-23 | PXD047423 | Pride

Transcriptomics in Zika virus-infected human brain organoids

Project description:PolyA+ RNA sequencing of Zika virus-infected human brain organoids at 5 days post-infection.

2017-04-03 | E-MTAB-4811 | biostudies-arrayexpress