Silk scaffolding drives self-assembly of functional and mature human brain organoids
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ABSTRACT:
PROVIDER: PRJNA837977 | ENA |
REPOSITORIES: ENA
Similar Datasets
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.
2022-05-17 | GSE202992 | GEO
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.
2022-02-12 | GSE196423 | GEO
Project description:Silk scaffolding drives self-assembly of functional and mature human brain organoids [scRNA-seq]
| PRJNA804881 | ENA
Project description:Silk scaffolding drives self-assembly of functional and mature human brain organoids [RNA-seq]
| PRJNA837980 | ENA
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 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 hPSCs 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 scaffold. Furthermore, oxygen sensing analysis showed that silk scaffolds create more favorable growth and differentiation conditions by facilitating the delivery of oxygen and nutrients. The silk scaffolding strategy appears to reduce intra-organoid variability and enhances self-organization into functionally mature human brain organoids.
| S-EPMC9614032 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-05-14 | GSE202993 | GEO
Project description:In this study, we sequenced four small RNA libraries derived from mature pollens, in vitro germinated pollens, mature silks and pollinated silks of maize, respectively. In total, 161 known miRNAs belonging to 27 families and 82 novel miRNAs were identified. Of them, miRNAs involved in pollen-silk (pistil) interactions were analyzed. On the male side, miRNA differentially expressed between mature and germinated pollen were identified, some of them participate in pollen germination and tube growth. On the female side, silk-expressed miRNAs respond to pollination were also responsive to stresses, especially drought and fungal invasion. Furthermore, GO analysis of target genes revealed that members related to anxin signal transduction and gene expressional regulation were overrepresented.The results indicated that during pollen-silk interactions, miRNAs-mediated auxin signal transduction plays important roles, and miRNAs took part in complex transcriptional regulating network.
2013-03-02 | GSE44787 | GEO
Project description:The inaccessibility of human tissue and the difficulty to achieve neuronal maturation and function in 2D cultures makes the study of human brain development, function and disease challenging. Here, we differentiated human pluripotent stem cells into three-dimensional (3D) regionalized human brain organoids which, when patterned towards a ventral midbrain (VM) fate, gave rise to mature and functional pigmented dopamine (DA) neurons. Using single cell transcriptomics, we defined the cellular composition and reconstructed the developmental trajectory of the different cell types, including DA neurons, by analyzing 120,000 cells harvested at different time points during differentiation. We also obtained an unbiased and comprehensive characterization of human DA subgroups, which reveals a molecular signature of DA neuron diversity and provides a valuable asset for the design of more targeted and effective stem-cell based therapies in Parkinson´s disease. However, the value of brain organoids in modeling later developmental stages and more mature neurons in a dish is hampered by their poor reproducibility and incomplete maturation. To address this issue, we designed a novel technological approach to generate bioengineered VM organoids supported by recombinant spider silk microfibers functionalized with full-length human laminin. Silk-VM organoids reproduce key molecular aspects of DA neurogenesis and, unlike conventional 3D culture, sustain the generation of functional DA neurons homogeneously throughout the organoid. Silk-VM organoids represent a significant advancement in the field of 3D culture, by better recapitulating physiologically relevant aspects of developing human brain tissue and thus paving the way toward their use in developmental studies as well as in in vitro disease modeling and drug discovery.
2021-10-29 | GSE168323 | GEO
Project description:In this study, we sequenced four small RNA libraries derived from mature pollens, in vitro germinated pollens, mature silks and pollinated silks of maize, respectively. In total, 161 known miRNAs belonging to 27 families and 82 novel miRNAs were identified. Of them, miRNAs involved in pollen-silk (pistil) interactions were analyzed. On the male side, miRNA differentially expressed between mature and germinated pollen were identified, some of them participate in pollen germination and tube growth. On the female side, silk-expressed miRNAs respond to pollination were also responsive to stresses, especially drought and fungal invasion. Furthermore, GO analysis of target genes revealed that members related to anxin signal transduction and gene expressional regulation were overrepresented.The results indicated that during pollen-silk interactions, miRNAs-mediated auxin signal transduction plays important roles, and miRNAs took part in complex transcriptional regulating network. Examination of 4 different tissues of maize to provide novel information for understanding the post-transcriptional regulations of pollen-pistil interactions
2013-03-02 | E-GEOD-44787 | biostudies-arrayexpress
Project description:To fully characterize the extent of genomic changes in senescent silk, we performed a time-course tissue harvesting. Material was collected at four time points: 3-, 7-, 11- and 15 days after silk emergence (DASE). Maize inbred line B104; 2 cm of basal part of silk from rings 6-10
2022-08-16 | E-MTAB-10847 | biostudies-arrayexpress