Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Generation of Regionally Specified Human Brain Organoids Resembling Thalamus Development.

ABSTRACT: Thalamus is a critical information relay hub in the cortex; its malfunction causes multiple neurological and psychiatric disorders. However, there are no model systems to study the development and function of human thalamus. Here, we present a protocol to generate regionally specified human brain organoids that recapitulate the development of the thalamus using human pluripotent stem cells (hPSCs). Thalamic organoids can be used to study human thalamus development, to model related diseases, and to discover potential therapeutics. For complete information on human thalamic organoids and their application, please refer to the paper by Xiang et al. (2019).

SUBMITTER: Xiang Y

PROVIDER: S-EPMC7580078 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Fusion of Regionally Specified hPSC-Derived Organoids Models Human Brain Development and Interneuron Migration.

Project description:Organoid techniques provide unique platforms to model brain development and neurological disorders. Whereas several methods for recapitulating corticogenesis have been described, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, has been lacking until recently. Here, we describe the generation of MGE and cortex-specific organoids from human pluripotent stem cells that recapitulate the development of MGE and cortex domains, respectively. Population and single-cell RNA sequencing (RNA-seq) profiling combined with bulk assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) analyses revealed transcriptional and chromatin accessibility dynamics and lineage relationships during MGE and cortical organoid development. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, fusing region-specific organoids followed by live imaging enabled analysis of human interneuron migration and integration. Together, our study provides a platform for generating domain-specific brain organoids and modeling human interneuron migration and offers deeper insight into molecular dynamics during human brain development.

| S-EPMC5720381 | biostudies-literature

Regionally specified human pluripotent stem cell-derived astrocytes

Project description:Bulk RNA-seq of highly pure regionally specified human pluripotent stem cell-derived astrocytes

2019-06-29 | GSE133489 | GEO

Cerebral organoids model human brain development and microcephaly.

Project description:The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.

| S-EPMC3817409 | biostudies-literature

Brain Organoids: Studying Human Brain Development and Diseases in a Dish.

Project description:With the rapid development of stem cell technology, the advent of three-dimensional (3D) cultured brain organoids has opened a new avenue for studying human neurodevelopment and neurological disorders. Brain organoids are stem-cell-derived 3D suspension cultures that self-assemble into an organized structure with cell types and cytoarchitectures recapitulating the developing brain. In recent years, brain organoids have been utilized in various aspects, ranging from basic biology studies, to disease modeling, and high-throughput screening of pharmaceutical compounds. In this review, we overview the establishment and development of brain organoid technology, its recent progress, and translational applications, as well as existing limitations and future directions.

| S-EPMC8448601 | biostudies-literature

Regionally specified human pluripotent stem cell-derived astrocytes exhibit different molecular signatures and functional properties.

Project description:Astrocytes display diverse morphologies in different regions of the central nervous system. Whether astrocyte diversity is attributable to developmental processes and bears functional consequences, especially in humans, is unknown. RNA-seq of human pluripotent stem cell-derived regional astrocytes revealed distinct transcript profiles, suggesting differential functional properties. This was confirmed by differential calcium signaling as well as effects on neurite growth and blood-brain barrier formation. Distinct transcriptional profiles and functional properties of human astrocytes generated from regionally specified neural progenitors under the same conditions strongly implicate the developmental impact on astrocyte diversity. These findings provide a rationale for renewed examination of regional astrocytes and their role in the pathogenesis of psychiatric and neurological disorders.

| S-EPMC6633609 | biostudies-literature

Rapid Generation of Regionally Specified CNS Neurons by Sequential Patterning and Conversion of Human Induced Pluripotent Stem Cells

Project description:The differentiation of patient-specific induced pluripotent stem cells (iPSCs) into specific neuronal subtypes has been exploited as an approach to modeling a variety of neurological disorders. However, achieving a highly pure population of neurons is challenging when using directed differentiation methods, especially for neuronal subtypes generated by complex and protracted protocols. In this study, we efficiently produced highly pure populations of regionally specified CNS neurons by using a modified NGN2-Puromycin direct conversion protocol. The protocol is amenable across a range of iPSC lines, with an efficiency above 97% by day 21, and above 95% of neurons positive for MAP2. This NGN2-Puromycin conversion resulted in a significant number of peripheral neurons, but by incorporating a short CNS patterning step, we eliminated these peripheral neurons. Furthermore, we used the patterning step to control the rostral-caudal identity. This approach to sequential patterning and NGN2-Puromycin conversion, when patterned with SMAD inhibitors, produced pure populations of forebrain neurons; when SMAD inhibitors and WNT agonists were applied, the approach produced anterior hindbrain excitatory neurons, resulting in a neuronal population containing VSX2/SHOX2 V2a interneurons. Overall, this sequential patterning and conversion protocol can be used for the production of a variety of CNS excitatory neurons from patient-derived iPSCs, which is a highly versatile system for investigating early disease events for a range of neurological disorders including Alzheimer's disease, motor neurons disease and spinal cord injury.

2020-06-24 | GSE149864 | GEO

Generation of human brain region-specific organoids using a miniaturized spinning bioreactor.

Project description:Human brain organoids, 3D self-assembled neural tissues derived from pluripotent stem cells, are important tools for studying human brain development and related disorders. Suspension cultures maintained by spinning bioreactors allow for the growth of large organoids despite the lack of vasculature, but commercially available spinning bioreactors are bulky in size and have low throughput. Here, we describe the procedures for building the miniaturized multiwell spinning bioreactor Spin? from 3D-printed parts and commercially available hardware. We also describe how to use Spin? to generate forebrain, midbrain and hypothalamus organoids from human induced pluripotent stem cells (hiPSCs). These organoids recapitulate key dynamic features of the developing human brain at the molecular, cellular and structural levels. The reduction in culture volume, increase in throughput and reproducibility achieved using our bioreactor and region-specific differentiation protocols enable quantitative modeling of brain disorders and compound testing. This protocol takes 14-84 d to complete (depending on the type of brain region-specific organoids and desired developmental stages), and organoids can be further maintained over 200 d. Competence with hiPSC culture is required for optimal results.

| S-EPMC6241211 | biostudies-literature

Fusion of Human Brain Organoids Assembles Bidirectional Connectivity Between Thalamus and Cortex

Project description:Human brain organoid techniques have rapidly advanced to facilitate investigating human brain development and diseases. Recent reports in generation and fusion of regionally defined brain organoids provide further opportunities to investigate the specific brain domains and their interactions. Focus of brain organoids has been to generate telencephalon due to its direct relevance in a variety of forebrain disorders. Despite its importance as a relay hub between cortex and peripheral tissues, the investigation of three-dimensional (3D) organoid model for the human thalamus has not yet been explored. Here, we describe a method to differentiate human embryonic stem cells (hESCs) to the thalamic organoids (hThOs) that specifically recapitulate the development of thalamus. Single-cell RNA sequencing (scRNA-seq) revealed a formation of distinct thalamic lineage cells, a lineage divergence from telencephalic lineage. Importantly, we developed a 3D system to create the reciprocal projections between thalamus and cortex by fusing the two distinct region-specific organoids representing the developing thalamus or cortex. Our study provides a platform for understanding human thalamic development and modeling circuit organizations and related disorders in the brain.

2018-12-20 | GSE122342 | GEO

Comparison of neuroepithelial cells and regionally specified astrocytes from human embryonic stem cells

Project description:These arrays were conducted in order to confirm the generation of astrocytes from human embryonic stem cells and to determine expression differences between astrocyte subtypes.

2009-11-11 | GSE18959 | GEO

Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

Project description:Neural stem/progenitor cells (NSC) have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ) of the adult brain. It is not known whether NSC can be found in all parts of the developing mid-trimester central nervous system (CNS) when the brain undergoes massive transformation and growth. Multipotent NSC from the mid-trimester cerebra, thalamus, SVZ, hippocampus, thalamus, cerebellum, brain stem and spinal cord can be derived and propagated as clonal neurospheres with increasing frequencies with increasing gestations. These NSC can undergo multi-lineage differentiation both in vitro and in vivo, and engraft in a developmental murine model. Regionally-derived NSC are phenotypically distinct, with hippocampal NSC having a significantly higher neurogenic potential (53.6%) over other sources (range of 0%-27.5%, p<0.004). Whole genome expression analysis showed differential gene expression between these regionally-derived NSC, which involved the Notch, epidermal growth factor as well as interleukin pathways. We have shown the presence of phenotypically-distinct regionally-derived NSC from the mid-trimester CNS, which may reflect the ontological differences occurring within the CNS. Aside from informing on the role of such cells during fetal growth, they may be useful for different cellular therapy applications.

| S-EPMC4152177 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data