Neural tRNA Expression Patterns in Brain Organoids
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PROVIDER: PRJNA1080535 | ENA |
REPOSITORIES: ENA
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Project description:Transfer RNAs (tRNAs) are traditionally known for their role in protein translation, yet recent discoveries highlight their broader functions in gene regulation, particularly through tRNA-derived small RNAs (tDRs). Studies have shown the singular importance of one unique ArgUCU tRNA isodecoder in mouse neural development, yet potential function(s) of tDRs derived from this and all other tRNAs remain largely unexplored in early human brain development. In this study, we employed cerebral cortical organoid models and AlkB-facilitated RNA methylation sequencing (ARM-seq) to profile tDRs across distinct stages of early human cerebral cortex development. Our analysis reveals dynamic expression patterns of diverse tDR groups derived from a wide range of isodecoders, with several distinct groups showing neural-specific expression. Computational analyses of these tDRs shows biased sequence motifs in over-represented tRNAs that are enriched with particular RNA modifications, giving initial clues to traits that change within the pool of tDRs during neural development. This expanded catalog of tDRs provides a framework for future studies on tRNA function in brain development and offers a deeper understanding of the complexity of tDR dynamics in neural differentiation.
2025-01-13 | GSE259250 | GEO
Project description:<p>Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an <em>in vitro</em> system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain organoids. We present an optimized and validated sample preparation protocol, including sample fixation, optimal embedding solution, homogenous deposition of matrices, data acquisition and processing to maximize the molecular information derived from mass spectrometry imaging. We focus on lipids in organoids, as they play critical roles during cellular and brain development. Using high spatial and mass resolution in positive- and negative-ion modes, we detected 260 lipids in the organoids. Seven of them were uniquely localized within the neurogenic niches or rosettes as confirmed by histology, suggesting their importance for neuroprogenitor proliferation. We observed a particularly striking distribution of ceramide-phosphoethanolamine CerPE 36:1; O2 restricted within rosettes and of phosphatidyl-ethanolamine PE 38:3, which was distributed throughout the organoid tissue but not in rosettes. This suggests that ceramide in this particular lipid species might be important for neuroprogenitor biology, while its removal may be important for terminal differentiation of their progeny. Overall, our study establishes the first optimized experimental pipeline and data processing strategy for mass spectrometry imaging of human brain organoids, allowing direct comparison of lipid signal intensities and distributions in these tissues. Further, our data shed new light on the complex processes that govern brain development by identifying specific lipid signatures that may play a role in metabolic cell fate trajectories. mass spectrometry imaging thus has great potential in advancing our understanding of early brain development as well as disease modeling and drug discovery.</p>
2023-05-23 | MTBLS7565 | MetaboLights
Project description:Developing platforms for ex vivo studies of human brain development and formulation of therapeutic strategies for a variety of conditions and diseases has been hampered by limited access to relevant human tissue and the necessity of using rodent models that imperfectly recapitulate human brain physiology. A promising advance is brain organoids that, to a greater extent than monolayer or spheroid cultures, recapitulate to varying extents the patterns of cell differentiation and morphological development characteristic of human brain. Here, we present an organoid-based research platform initiated using L-MYC immortalized human fetal neural stem cells (NSCs) (LMNSC01), and) and grown in a physiological 4% oxygen environment similar that in developing brain. Expanded LMNSC01 cells maintain genomic stability and multipotency, and are non-tumorigenic. Using authentic human NSCs as starting material eliminates the ex vivo programming and reprogramming required to achieve directed differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). LMNSC008 brain organoids were characterized using NanoString technology to profile gene expression for over 120 days in vitro and comparing these patterns to these same genes during normal brain development (BrainSpan database). We also visualized by immunofluorescence changes in expression and distribution of genes representative of these developmental processes along with morphological changes occurring over this same period. We observe parallel developmental patterns of gene expression between organoids and developing cortex for pathways involved in neuronal cytoskeleton, neuron-glia interaction, neural connectivity, neurotransmission, metabolism, axon and dendrite structure, tissue integrity, angiogenesis, and myelination. We suggest that LMNSC01 organoids offer an alternative to the challenges of iPSC programming and neural induction. Notable properties of this platform are its initiation with a line of authentic neural stem cells (LMNSC01), the consistency of the organoids produced, and favorable comparison of their gene expression patterns with those observed during normal fetal development.
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2023-03-11 | PXD026381 | Pride
Project description:Organoids have been widely used as unique models of human brain development and disorders. However, the lack of vasculatures in brain orgnoids limits their application in the study of brain vasculature development and diseases. Here, we described to the generation of vascularized brain organoids (VBOrs) with different brain regions from human embryonic stem cells. The goals of this study are to analyze the cell populations of the new model of vasularized brain organoids cultured from human embryonic stem cells (H9). We found that VBOrs contain variant brain cells inculding neural progenitors, neuronal cells, astrocytes, sparse endothelial cells, and pericytes. The new model of VBOrs should be valuable for addressing questions between brain vasculatures and neural cells.
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