A fully defined protocol for differentiation of human pluripotent stem cells into forebrain neural progenitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE131697 | GEO | 2020/01/14
REPOSITORIES: GEO
Similar Datasets
Project description:A fully defined protocol for differentiation of human pluripotent stem cells into forebrain neural progenitors
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Project description:This bulk RNAseq dataset is part of a dataset described in the manuscript titled "Fully defined NGN2 neuron protocol reveals diverse signatures of neuronal maturation". This dataset includes NPC derived neurons using a wild type iPSC line, and was used to validate a MS-117 maturation score which attempt to establish a socre system to assess neuronal maturation with iPSCs derived neurons.
2024-09-13 | GSE266359 | GEO
Project description:The forebrain has expanded in size and complexity during hominoid evolution. The contribution of post-transcriptional control of gene expression to this process is unclear. Using in-depth proteomics in combination with bulk and single-cell RNA sequencing, we analyzed protein and RNA levels of almost 5,000 genes in human and chimpanzee forebrain neural progenitor cells. We found that species differences in protein expression level was often independent of RNA levels, and more frequent than transcriptomic differences. Low-abundant proteins were more likely to show species-specific expression levels, while proteins expressed at a high level appeared to have evolved under stricter constraints. Our study implicates a previously unappreciated broad and important role for post-transcriptional regulatory mechanisms in the evolution of the human forebrain.
2021-12-31 | GSE127253 | GEO
Project description:Post-transcriptional mechanisms distinguish human and chimpanzee forebrain progenitors
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Project description:Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multilayered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice. Twelve E9.5 wildtype forebrain samples were compared to four E9.5 Vegf120 mouse forebrains, four E9.5 Vegf188 mouse forebrains, three E9.5 Vegf120/188 mouse forebrains, and four E11.5 wild type forebrains using the Mouse 430. 2.0 Affymetrix GeneChip. This study comprises of new samples and reanalysis of Samples from GSE30767 and GSE8091.
2013-11-21 | E-GEOD-52542 | biostudies-arrayexpress
Project description:RNA-seq samples from 3 species across a differentiation from induced pluripotent stem cells to neural progenitor cells were generated to study gene expression evolution. Briefly, previously generated urinary stem cell derived iPSCs of 3 human (Homo sapiens) individuals (3 clones), 1 gorilla (Gorilla gorilla) individual and fibroblast derived cynomolgus macaque (Macaca fascicularis) iPSCs of 2 individuals (4 clones) (Geuder et al. 2021) were differentiated to neural progenitor cells via dual-SMAD inhibition as three-dimensional aggregation culture (Chambers et al. 2009; Ohnuki et al. 2014). Bulk RNA-seq libraries of iPSCs and NPCs were generated using prime-seq protocol (Janjic et al. 2022).
2023-11-23 | E-MTAB-13494 | biostudies-arrayexpress
Project description:We have generated transgenic mice with tetracycline-regulated conditional expression of a constitutively active allele of FoxO3 under the control of the forebrain-specific CaMKIIa promoter. In adult animals, there was a reduction of brain weight by 30% and an almost complete loss of the dorsal dentate gyrus with normal cortical layering. Interestingly, the adult mice showed motor hyperactivity and a selective loss of long-term memory with normal spatial learning. We observed enhanced apoptosis starting from day E10.5. Performing microarray expression analyses and Q-PCR validation with E12.5 forebrain RNA, we observed an over-representation of thalamic markers and an under-representation of cortical markers in transgenic as compared to control animals. Immunohistochemical data show a loss of progenitors in the lateral ventricles. Up-regulation of Pik3ip1 as a target gene of FoxO3 could be responsible for the observed increase in apoptosis. The obtained forebrain expression signature is reminiscent of a Pax6 knockdown phenotype showing that expression of this FoxO3 allele during development affected neural progenitor survival and overall brain development. Conclusion: Neural progenitors are vulnerable to constitutively active FoxO3-induced apoptosis. We sought to determine the transcriptional differences in forebrains from E12.5 mice expressing a constitutively active alleleof FoxO3 under the control of the forebrain-specific CaMKIIa promoter. To this end two time-pregnant dams were sacrificed 12 days after the vaginal plug was detected, and the embryos were prepared. Visual staging of the embryos confirmed their age. Genotyping and luciferase measurements were performed in order to assess presence and acitivity of the transgenes.
2012-09-13 | E-GEOD-21089 | biostudies-arrayexpress
Project description:Regulation of neural stem cell (NSC) fate decisions is critical during the transition from a multicellular mammalian forebrain neuroepithelium to the multilayered neocortex. Forebrain development requires coordinated vascular investment alongside NSC differentiation. Vascular endothelial growth factor A (Vegf) has proven to be a pleiotrophic gene whose multiple protein isoforms regulate a broad range of effects in neurovascular systems. To test the hypothesis that the Vegf isoforms (120, 164, and 188) are required for normal forebrain development, we analyzed the forebrain transcriptome of mice expressing specific Vegf isoforms, Vegf120, VegfF188, or a combination of Vegf120/188. Transcriptome analysis identified differentially expressed genes in embryonic day (E) 9.5 forebrain, a time point preceding dramatic neuroepithelial expansion and vascular investment in the telencephalon. Meta-analysis identified gene pathways linked to chromosome-level modifications, cell fate regulation, and neurogenesis that were altered in Vegf isoform mice.
2013-11-21 | GSE52542 | GEO
Project description:BackgroundDifferentiation of pluripotent stem cells in vitro provides a powerful means to investigate early developmental fates, including hematopoiesis. In particular, the use of a fully defined medium (FDM) would avoid biases induced by unidentified factors contained in serum, and would also allow key molecular mediators involved in such a process to be identified. Our goal was to induce in vitro, the differentiation of human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) into morphologically and phenotypically mature leukocytes and erythrocytes, in the complete absence of serum and feeder cells.Methodology/principal findingsESC and iPSC were sequentially induced in liquid cultures for 4 days with bone morphogenic protein-4, and for 4 days with FLT3-ligand, stem cell factor, thrombopoietin and vascular endothelium growth factor. Cell differentiation status was investigated by both mRNA expression and FACS expression profiles. Cells were further sorted and assayed for their hematopoietic properties in colony-forming unit (CFU) assays. In liquid cultures, cells progressively down-modulated Oct-4 expression while a sizeable cell fraction expressed CD34 de novo. SCL/Tal1 and Runx1 transcripts were exclusively detected in CD34(+) cells. In clonal assays, both ESC and iPSC-derived cells generated CFU, albeit with a 150-fold lower efficacy than cord blood (CB) CD34(+) cells. ESC-derived CD34(+) cells generated myeloid and fully hemoglobinized erythroid cells whereas CD34(-) cells almost exclusively generated small erythroid colonies. Both ESC and iPSC-derived erythroid cells expressed embryonic and fetal globins but were unable to synthesize adult ?-globin in contrast with CB cells, suggesting that they had differentiated from primitive rather than from definitive hematopoietic progenitors.Conclusions/significanceShort-term, animal protein-free culture conditions are sufficient to sustain the differentiation of human ESC and iPSC into primitive hematopoietic progenitors, which, in turn, produce more mature blood cell types. However, additional factors have yet to be identified to allow their differentiation into definitive erythroid cultures.
| S-EPMC3045374 | biostudies-literature
Project description:NGN2-driven iPSC-to-neuron conversion is a popular method for human neurological disease modeling. In this study, we report a fully standardized approach for generating functional excitatory cortical neurons. This method utilizes clonal, targeted-engineered iPSC lines and employs fully defined reagents. We demonstrate that our protocol generates consistent excitatory cortical neurons at scale. Comprehensive temporal omics, electrophysiological, and morphological profilings indicate the continued progression of neuronal maturation for at least 150 days. Deep quantitative characterizations through transcriptomic, imaging, and functional assays reveal coordinated actions of multiple pathways driving neuronal maturation. The neurons express the majority of the key risk genes in Alzheimer's disease, Parkinson's disease, and autism, demonstrating the relevance of our protocol in modeling human neurological disorders. This well-defined method, profiling data, and functional characterization provide a solid and reliable framework for developing human in vitro neuronal models for disease modeling.
2023-10-18 | MSV000093150 | MassIVE