Functional neuronal circuitry and oscillatory dynamics in human brain organoids
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA856997 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Nested oscillatory dynamics in cortical organoids model early human brain network development
| PRJNA534424 | ENA
Project description:We characterized the different cell types and their differential gene expression patterns in 1, 3, 6, and 10 month-old cortical organoids.
2019-04-25 | GSE130238 | GEO
Project description:Nervous system (NS) development relies on coherent up-regulation of extensive sets of genes in a precise spatiotemporal manner. How such transcriptome-wide effects are orchestrated at the molecular level remains an open question. Here we show that 3’-untranslated regions (3’UTRs) of multiple neuronal transcripts contain A/U-rich cis-elements (AREs) recognized by tristetraprolin (TTP/Zfp36), an RNA-binding protein previously reported to destabilize mRNAs encoding predominantly cytokines, growth factors and proto-oncogenes. We further demonstrate that the efficiency of ARE-dependent mRNA degradation declines during neural differentiation due to a decrease in the TTP protein expression mediated by the NS-enriched microRNA miR-9. Our experiments with transgenenic cell lines suggest that TTP down-regulation is essential for proper neuronal differentiation. Moreover, inactivation of TTP in neuroblastoma cells or mouse embryonic fibroblasts induces major changes in their transcriptomes accompanied by significantly elevated expression of NS-specific genes. We conclude that the newly identified miR-9/TTP circuitry limits unscheduled accumulation of neuronal mRNAs in non-neuronal cells and ensures coordinated up-regulation of these transcripts in neurons. 3'READS of undifferentiated and 3.5-day differentiated P19 cells
2015-04-01 | E-GEOD-61098 | biostudies-arrayexpress
Project description:Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids
| PRJNA578385 | ENA
Project description:Brain organoids are promising tools for disease modelling and drug development. For proper neuronal network formation excitatory and inhibitory neurons as well as glia need to co-develop. Here we report the directed differentiation and self-organization of induced pluripotent stem cells in a collagen hydrogel towards a highly interconnected neuronal network in a macroscale tissue format. Bioengineered Neuronal Organoids (BENOs) comprise interconnected excitatory and inhibitory neurons as well as supportive astrocytes and oligodendrocytes. Giant depolarizing potential (GDP)-like events observed within 20-40 days of BENO culture mimic early network activity of the fetal brain. The switch from excitatory to inhibitory GABA activity, and reduced GDPs at >40 day BENO cultures indicate progressive neuronal network maturation. BENOs demonstrate expedited complex network burst development after two months of culture and provide the first evidence for long-term potentiation and plasticity in brain organoids. BENOs exhibit structural and functional properties similar to the fetal brain and thus may be explored as a model to study the development of neuronal plasticity.
2020-07-02 | GSE139101 | GEO
Project description:iPSC-derived microglia export cholesterol to neuronal cells in human brain organoids and promote their maturation
2023-05-19 | PXD042344 | JPOST Repository
Project description:During somitogenesis, oscillatory expression of genes in the notch and wnt signaling pathways plays a key role in regulating segmentation. These oscillations in expression levels are elements of a species-specific developmental mechanism. To date, the periodicity and components of the human clock remain unstudied. Here we show that a human mesenchymal stem/stromal cell (MSC) model can be induced to display oscillatory gene expression. We observed that the known cycling gene HES1 oscillated with a 5 hour period, consistent with available data on the rate of somitogenesis in humans. We also observed cycling of Hes1 expression in mouse C2C12 myoblasts with a period of 2 hours, consistent with previous in vitro and embryonic studies. Furthermore, we used microarray and quantitative PCR (Q-PCR) analysis to identify additional genes that display oscillatory expression both in vitro and in mouse embryos. We confirmed oscillatory expression of the notch pathway gene Maml3 and the wnt pathway gene Nkd2 by whole mount in situ hybridization analysis and Q-PCR. Expression patterns of these genes were disrupted in Wnt3atm1Amc mutants but not in Dll3pu mutants. Our results demonstrate that human and mouse in vitro models can recapitulate oscillatory expression observed in embryo and that a number of genes in multiple developmental pathways display dynamic expression in vitro. Keywords: time series
2007-05-01 | GSE7012 | GEO
Project description:Nervous system (NS) development relies on coherent up-regulation of extensive sets of genes in a precise spatiotemporal manner. How such transcriptome-wide effects are orchestrated at the molecular level remains an open question. Here we show that 3’-untranslated regions (3’UTRs) of multiple neuronal transcripts contain A/U-rich cis-elements (AREs) recognized by tristetraprolin (TTP/Zfp36), an RNA-binding protein previously reported to destabilize mRNAs encoding predominantly cytokines, growth factors and proto-oncogenes. We further demonstrate that the efficiency of ARE-dependent mRNA degradation declines during neural differentiation due to a decrease in the TTP protein expression mediated by the NS-enriched microRNA miR-9. Our experiments with transgenenic cell lines suggest that TTP down-regulation is essential for proper neuronal differentiation. Moreover, inactivation of TTP in neuroblastoma cells or mouse embryonic fibroblasts induces major changes in their transcriptomes accompanied by significantly elevated expression of NS-specific genes. We conclude that the newly identified miR-9/TTP circuitry limits unscheduled accumulation of neuronal mRNAs in non-neuronal cells and ensures coordinated up-regulation of these transcripts in neurons.
2015-04-01 | GSE61098 | GEO
Project description:Klotho inhibits neuronal senescence in human brain organoids
| PRJNA720649 | ENA