Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA284107 | ENA |
REPOSITORIES: ENA
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Project description:There are a total of four samples each for this analysis. Each sample consists of the cells grown on three 10 cm culture plates. Each plate should have 2x106 cells for a total of 6x106 cells per sample when all three plates are combined. The first sample is undifferentiated human embryonic stem cells, the second sample is human glutamatergic neurons derived from those human embryonic stem cells, the third sample is undifferentiated human induced pluripotent stem cells and the fourth sample is human glutamatergic neurons derived from those human induced pluripotent stem cells.
2017-06-19 | ST000768 | MetabolomicsWorkbench
Project description:Biallelic mutations in the gene that encodes the enzyme N-glycanase 1 (NGLY1) cause a rare disease with multi-symptomatic features including developmental delay, intellectual disability, neuropathy and seizures. NGLY1’s activity in human neural cells is currently not well understood. To understand how NGLY1 gene loss leads to the specific phenotypes of NGLY1 deficiency, we employed direct conversion of NGLY1 patient-derived induced pluripotent stem cells (iPSCs) to functional cortical neurons. Transcriptomic, proteomic, and functional studies of iPSC-derived neurons lacking NGLY1 function revealed several major cellular processes that were altered, including protein aggregate-clearing functionality, mitochondrial homeostasis, and synaptic dysfunctions. These phenotypes were rescued by introduction of a functional NGLY1 gene and were observed in iPSC-derived mature neurons, but not astrocytes. Finally, laser capture microscopy followed by mass spectrometry provided detailed characterization of the composition of protein aggregates specific to NGLY1-deficient neurons. Future studies will harness this knowledge for therapeutic development.
2024-05-23 | PXD031091 | Pride
Project description:Alginate-based 3D culture of human induced pluripotent stem cells and their differentiation to functional dopaminergic neurons
| PRJNA740008 | ENA
Project description:Astrocytes regulate the functional maturation of neurons by providing trophic support, regulating membrane properties and coordinating synapse formation. However, it is unclear to what degree astrocytes use activity-dependent mechanisms in these intercellular signalling processes. Using an induced pluripotent stem cell system and long-term optogenetic stimulation of human astrocytes, we reveal that activity-dependent astrocytic signals enhance the functional maturation of human cortical neurons, through increases in synaptic connectivity and excitability. Transcriptomic analyses determine that this involves the activity-dependent up-regulation of cholesterol synthesis – a process ascribed to astrocytes, which regulates neuronal maturation. Up-regulated astrocyte genes encode enzymes and transcription factors that control the levels of cholesterol synthesis. Biochemical assays confirm an activity-dependent upregulation of cholesterol synthesis in astrocytes, which is required for the maturational effects upon neurons. Thus, we reveal a novel mechanism that may dynamically match astrocyte function to neuronal needs, and identify targets for modulating cholesterol synthesis in the CNS.
2023-07-21 | GSE236398 | GEO
Project description:We have assessed the importance of SQSTM1 in human induced pluripotent stem cell (iPSC)-derived cortical neurons with and without SQSTM1. By combining high-content imaging, RNA-Seq, and functional mitochondrial readouts, we showed that SQSTM1 depletion causes aberrations in mitochondrial gene expression and functionality in iPSC-derived neurons.
2021-01-18 | E-MTAB-9383 | biostudies-arrayexpress
Project description:FIP200 (also known as RB1CC1) has been implicated in a number of psychiatric disorders. The current project aims to characterize the membranomic changes in neurons due to FIP200 loss of function. To this end, two isogenic human pluripotent stem cell (hPSC) lines with FIP200 KO mutations in exon 4 were generated using CRISPR-Cas9-mediated genome editing. The resulting KO clones, together with control lines, were then forward programmed into neurons by overexpression of NGN2, followed by co-culture on mouse astrocytes for 3 weeks before harvesting the cells for MS analysis.
2023-04-05 | MSV000091643 | MassIVE
Project description:Cerebral organoids (CerOrgs) derived from human induced pluripotent stem cells (iPSCs) are a valuable tool to study human astrocytes and their interaction with neurons and microglia. The timeline of astrocyte development and maturation in this model is currently unknown and this limits the value and applicability of the model. Therefore, we generated CerOrgs from three healthy individuals and assessed astrocyte maturation after 5, 11, 19, and 37 weeks in culture. At these four time points, the astrocyte lineage was isolated based on the expression of integrin subunit alpha 6 (ITGA6). Based on the transcriptome of the isolated ITGA6-positive cells, astrocyte development started between 5 and 11 weeks in culture and astrocyte maturation commenced after 11 weeks in culture. After 19 weeks in culture, the ITGA6-positive astrocytes had the highest expression of human mature astrocyte genes, and the predicted functional properties were related to brain homeostasis. After 37 weeks in culture, a subpopulation of ITGA6-negative astrocytes appeared highlighting the heterogeneity within the astrocytes. The morphology shifted from an elongated progenitor-like morphology to the typical bushy astrocyte morphology. Based on the morphological properties, predicted functional properties, and the similarities with the human mature astrocyte transcriptome, we concluded that ITGA6+ astrocytes have developed optimally in 19-week-old CerOrgs.
2023-10-10 | GSE244778 | GEO
Project description:Cellular plasticity is a prerequisite to adapt to ever-changing stimuli. Therefore, cells constantly reshape their translatome and, in turn, their proteome. The control of translational activity has been extensively studied at the stage of translation initiation. How cells regulate polysome speed is, however, widely unknown. Here, we exploited a kinetic approach to investigate global translation kinetics in cells. We found that polysome speeds differ between different cell types including astrocytes, induced pluripotent human stem cells, human neural stem cells, and human and rat neurons. Among these cells, we observed that mature cortical neurons translate the fastest. This finding was even more striking as these cells express the elongation factor 2 (eEF2) at lowest levels compared to other cell types. We found that neurons resolve this obstacle by inactivating a fraction of their ribosomes. This process is regulated by the levels and phosphorylation of eEF2 as well as by NMDA mediated neuronal stimulation. Our data strongly suggest a novel regulation mechanism in which nerve cells inactivate ribosomes to allow for translational remodeling. This finding has important implications for developmental brain disorders that are hallmarked by altered translation.
2024-05-10 | PXD043207 | Pride
Project description:Reliability of 3D Cortical Spheroids Generation from Human Pluripotent Stem Cells
| PRJNA494166 | ENA
Project description:Meaningful models of human neural development and neurodegeneration are extremely important when exploring stem-cell-based regenerative therapies. However, existing 3D cultures fall short of being highly defined, modular, and controllable. Adapting a glycosaminoglycan-based, cell-responsive hydrogel platform, we stimulated primary and induced human neural stem cells (NSCs) to manifest neurogenic plasticity and form extensive neuronal networks in vitro. The 3D cultures exhibited neurotransmitter responsiveness, electrophysiological activity, and tissue-specific extracellular matrix (ECM) deposition. By whole transcriptome sequencing, we identified that 3D cultures express mature neuronal markers, and reflect the in vivo genetic program of mature cortical neurons compared to 2D cultures. Thus, our data suggest that our established 3D hydrogel culture supports the tissue-mimetic maturation of human neurons in an unprecedented manner. We modeled neurodegenerative conditions by treating the cultures with A?42 peptide and observed the known human pathological effects of Alzheimer?s disease including reduced NSC proliferation, impaired neuronal network formation, synaptic loss and failure in ECM deposition as well as elevated Tau hyperphosphorylation and formation of neurofibrillary tangles. We also determined the changes in transcriptomes of primary and induced NSC-derived neurons after A?42, providing a useful resource for further studies. Thus, our hydrogel-based human cortical 3D cell culture is a powerful platform for studying various aspects of neural development and neurodegeneration, as exemplified for A?42 toxicity and neurogenic stem cell plasticity.
2020-01-01 | GSE78117 | GEO