Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA383338 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5454080.fastq.gz | Fastqsanger.gz | |||
| SRR5454090.fastq.gz | Fastqsanger.gz | |||
| SRR5454100.fastq.gz | Fastqsanger.gz | |||
| SRR5454081.fastq.gz | Fastqsanger.gz | |||
| SRR5454091.fastq.gz | Fastqsanger.gz |
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Project description:Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection
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Project description:Self-organized cerebral organoids with human specific features predict effective drugs to combat Zika virus infection [expression array]
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Project description:Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability and tissue heterogeneity limit accessibility and broad applications of current organoid technologies. Here we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and importantly, a distinct human-specific outer radial glia cell layer. We have also developed protocols to generate midbrain and hypothalamic organoids. Finally, we employed this forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed that preferential, productive ZIKA infection of cortical neural progenitors leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell layer volume that resembles microcephaly. Together, our brain region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human brain development and diseases, and for compound testing.
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Project description:Pluripotent stem cells (PSC) can differentiate inot any cell type of an organism. Their remarkable capability of self-organization enables the formation of three-dimensional structures that resembles miniature organs, including cerebral organoids. These organoids can recreate early steps of the human cerebral cortex development, and show great potential for modeling human diseases, particularly for those with a developmental component. This data evidences stem cell-derived cerebral organoids as a key model to study brain development and neurodevelopmental, neurodegenerative and neuropsychiatric diseases.
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Project description:Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional (3D) structures provide a unique opportunity to generate cytoarchitecture and cell-cell interactions reminiscent of human brain complexity in a dish. However, current in vitro brain organoid methodologies often result in intra-organoid variability, limiting their use in recapitulating later developmental stages as well as in disease modeling and drug discovery. In addition, cell stress and hypoxia resulting from long-term culture lead to incomplete maturation and cell death within the inner core. Here, we used a recombinant silk microfiber network as a scaffold to drive human PSCs to self-arrange into engineered cerebral organoids. Silk scaffolding promoted neuroectoderm formation and reduced heterogeneity of cellular organization within individual organoids. Bulk and single cell transcriptomics confirmed that silk cerebral organoids display more homogeneous and functionally mature neuronal properties than organoids grown in the absence of silk fibers. Furthermore, oxygen sensing analysis showed that silk scaffolds create more favorable growth and differentiation conditions by facilitating the delivery of oxygen and nutrients. Silk-engineering platform appears to reduce intra-organoid variability and enhances functional maturation during spontaneous self-patterning in human brain organoid differentiation.
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Project description:Human pluripotent stem cells (hPSCs) are intrinsically able to self-organize into cerebral organoids that mimic features of developing human brain tissue. These three-dimensional (3D) structures provide a unique opportunity to generate cytoarchitecture and cell-cell interactions reminiscent of human brain complexity in a dish. However, current in vitro brain organoid methodologies often result in intra-organoid variability, limiting their use in recapitulating later developmental stages as well as in disease modeling and drug discovery. In addition, cell stress and hypoxia resulting from long-term culture lead to incomplete maturation and cell death within the inner core. Here, we used a recombinant silk microfiber network as a scaffold to drive human PSCs to self-arrange into engineered cerebral organoids. Silk scaffolding promoted neuroectoderm formation and reduced heterogeneity of cellular organization within individual organoids. Bulk and single cell transcriptomics confirmed that silk cerebral organoids display more homogeneous and functionally mature neuronal properties than organoids grown in the absence of silk fibers. Furthermore, oxygen sensing analysis showed that silk scaffolds create more favorable growth and differentiation conditions by facilitating the delivery of oxygen and nutrients. Silk-engineering platform appears to reduce intra-organoid variability and enhances functional maturation during spontaneous self-patterning in human brain organoid differentiation.
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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).
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