Homo sapiens
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PROVIDER: PRJNA304502 | ENA |
REPOSITORIES: ENA
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Project description:Cerebral organoids â three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells â have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures. 734 single-cell transcriptomes from human fetal neocortex or human cerebral organoids from multiple time points were analyzed in this study. All single cell samples were processed on the microfluidic Fluidigm C1 platform and contain 92 external RNA spike-ins. Fetal neocortex data were generated at 12 weeks post conception (chip 1: 81 cells; chip 2: 83 cells) and 13 weeks post conception (62 cells). Cerebral organoid data were generated from dissociated whole organoids derived from induced pluripotent stem cell line 409B2 (iPSC 409B2) at 33 days (40 cells), 35 days (68 cells), 37 days (71 cells), 41 days (74 cells), and 65 days (80 cells) after the start of embryoid body culture. Cerebral organoid data were also generated from microdissected cortical-like regions from H9 embryonic stem cell derived organoids at 53 days (region 1, 48 cells; region 2, 48 cells) or from iPSC 409B2 organoids at 58 days (region 3, 43 cells; region 4, 36 cells).
2015-12-07 | E-GEOD-75140 | biostudies-arrayexpress
Project description:Cerebral organoids – three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells – have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.
2015-12-07 | GSE75140 | GEO
Project description:Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain
| PRJNA323702 | ENA
Project description:Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and gene regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. 74% of 35,627 demethylated regions identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development.
2016-12-20 | GSE82022 | GEO
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.
2024-04-21 | GSE248901 | GEO
Project description:Cerebral organoids have emerged as faithful humanoid avatars for modeling numerous advanced neurodevelopmental and pathological processes and additionally serve as a powerful discovery platform for less well-characterized neurobiological programs. Towards this later prospect, we leveraged mass spectrometry-based proteomics to molecularly profile precursor and more committed neural compartments of both human-derived organoids and mid-gestation fetal brain tissue to define overlapping protein-level programs. Interestingly, this included numerous precursor-enriched transcriptional regulatory proteins that were notably not found to be differentially expressed in previous transcriptomic datasets. Specifically, we show that the RuvB-like 2 (RUVBL2) AAA-type ATPase is preferentially expressed in the SOX2-positive compartment of organoids and chemical inactivation leads to precursor cell displacement and apoptosis within the more mature DCX-positive niche. To explore potential clinicopathological correlates of this disruption in organoid cytoarchitecture, we interrogated various clinical datasets, and identified de novo deletions, missense mutations and a novel recurring tandem duplication involving RUVBL2 in patients diagnosed with neurodevelopmental and autism spectrum disorders. Together, our study demonstrates how cell-type specific and phenotype-level profiling of cerebral organoids can help nominate and implicate previously unappreciated genes in neurodevelopment and disease.
2022-04-07 | PXD028911 | Pride
Project description:Cerebral organoids have emerged as faithful humanoid avatars for modeling neurodevelopmental and pathological processes. Additionally, they serve as powerful discovery platforms for less characterized neurobiological programs. Towards this prospect, we leveraged mass spectrometry-based proteomics to molecularly profile precursor and neural compartments of both human-derived organoids and mid-gestation fetal brain tissue, to define overlapping programs. Our analysis included precursor-enriched transcriptional regulatory proteins that were not found to be differentially expressed in previous transcriptomic datasets. To highlight the discovery potential of this resource, we show that RUVBL2 is preferentially expressed in the SOX2-positive compartment of organoids and chemical inactivation leads to precursor cell displacement and apoptosis. To explore clinicopathological correlates of this cytoarchitectural disruption, we interrogated clinical datasets, and identified rare de novo genetic variants involving RUVBL2 in patients with neurodevelopmental impairments. Together, our study demonstrates how cell-type specific profiling of organoids can help nominate previously unappreciated genes in neurodevelopment and disease.
2022-04-07 | PXD033012 | Pride
Project description:Outer radial glia (oRG) emerged during mammalian evolution as cortical progenitor cells that directly support the development of an enlarged outer subventricular zone (oSVZ) and, in turn, the expansion of the neocortex. The in vitro generation of oRG is essential to model and investigate the underlying mechanisms of human neocortex development and expansion. By activating the STAT3 pathway using LIF, which is not produced in guided cortical organoids, we developed a cerebral organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ. The structured oSVZ is composed of progenitor cells expressing specific oRG markers such as GFAP, LIFR, HOPX and closely matching human oRG in vivo. In this microenvironment, cortical neurons showed faster maturation with enhanced metabolic and functional activity. Incorporation of hPSC-derived brain vascular LIF-producing pericytes in cerebral organoids mimicked the effects of LIF treatment. These data indicate that the cellular complexity of the cortical microenvironment, including cell types of the brain vasculature, favors the appearance of oRG and provides a platform to routinely study oRG in hPSC-derived brain organoids.
2024-04-15 | GSE224346 | GEO
Project description:Brain organoids derived from human pluripotent stem cells recapitulate the course of human brain development. We applied proteomic analysis to human brainstem organoids which were developed by a novel method.
2020-05-01 | PXD016807 | JPOST Repository
Project description:Human neocortex expansion likely contributed to the remarkable cognitive abilities of humans. This expansion is thought to primarily reflect differences in proliferation versus differentiation of neural progenitors during cortical development. Here, we have searched for such differences by analysing cerebral organoids from human and chimpanzees using immunohistochemistry, live imaging, and single-cell transcriptomics. We find that the cytoarchitecture, cell type composition, and neurogenic gene expression programs of humans and chimpanzees are remarkably similar. Notably, however, live imaging of apical progenitor mitosis uncovered a lengthening of prometaphase-metaphase in humans compared to chimpanzees that is specific to proliferating progenitors and not observed in non-neural cells. Consistent with this, the small set of genes more highly expressed in human apical progenitors points to increased proliferative capacity, and the proportion of neurogenic basal progenitors is lower in humans. These subtle differences in cortical progenitors between humans and chimpanzees may have consequences for human neocortex evolution.
2016-11-04 | GSE86207 | GEO