D4899051-7c09-4710-897b-9de4cef2f0e3 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001008746 | EGA |
REPOSITORIES: EGA
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Project description:We generated a single-cell RNA-seq atlas capturing over 100,000 cells spanning all stages of the mouse cerebral development. By examining data from over 100 cerebral tumour samples, our study reveals that, despite the phenotypic/genotypic differences between the tumour types, they are all comprised of developmental sublineages that map most closely to embryonic or juvenile stages of development.
| EGAS00001006237 | EGA
Project description:We map the development of mouse cerebrum across the developmental time-course, from embryonic day 12.5 to postnatal day 365, performing single-cell transcriptomics on >100,000 cells. By comparing this reference atlas to single-cell data from >100 glial tumours of the adult and pediatric human cerebrum, we find that tumour cells have an expression signature that overlaps with temporally restricted, embryonic radial glial precursors (RGPs) and their immediate sublineages. Further, we demonstrate that transformation of early RGPs in a genetic mouse model gives rise to adult cerebral tumours that show an embryonic/juvenile RGP identity. Together, these findings implicate the acquisition of embryonic-like states in the genesis of adult glioma, providing insight into the origins of human glioma, and identifying specific developmental cell types for therapeutic targeting.
2022-06-14 | GSE200202 | GEO
Project description:The cerebral cortex is a pivotal structure that is integral to advanced brain functions within the mammalian central nervous system. Patterns of DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5'- hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in early stages can profoundly alter the epigenetic regulation program, which provides new insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.
2022-10-31 | GSE215230 | GEO
Project description:The cerebral cortex is a pivotal structure that is integral to advanced brain functions within the mammalian central nervous system. Patterns of DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5'- hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in early stages can profoundly alter the epigenetic regulation program, which provides new insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.
2022-10-31 | GSE215229 | GEO
Project description:The cerebral cortex is a pivotal structure that is integral to advanced brain functions within the mammalian central nervous system. Patterns of DNA methylation and hydroxymethylation play important roles in regulating cerebral cortex development. However, it remains unclear whether abnormal cerebral cortex development, such as microcephaly, could rescale the epigenetic landscape, potentially contributing to dysregulated gene expression during brain development. In this study, we characterize and compare the DNA methylome/hydroxymethylome and transcriptome profiles of the cerebral cortex across several developmental stages in wild-type (WT) mice and Mcph1 knockout (Mcph1-del) mice with severe microcephaly. Intriguingly, we discover a global reduction of 5'- hydroxymethylcytosine (5hmC) level, primarily in TET1-binding regions, in Mcph1-del mice compared to WT mice during juvenile and adult stages. Notably, genes exhibiting diminished 5hmC levels and concurrently decreased expression are essential for neurodevelopment and brain functions. Additionally, genes displaying a delayed accumulation of 5hmC in Mcph1-del mice are significantly associated with the establishment and maintenance of the nervous system during the adult stage. These findings reveal that aberrant cerebral cortex development in early stages can profoundly alter the epigenetic regulation program, which provides new insights into the molecular mechanisms underpinning diseases related to cerebral cortex development.
2022-10-31 | GSE215228 | GEO
Project description:To explore the early steps in glioma formation, we utilized conditional gene deletion and lineage tracing in tumour mouse models, coupled with serial magnetic resonance imaging to initiate and then closely track tumour formation. We isolated labeled and unlabeled cells at multiple stages -- before the first visible abnormality, at the time of the first visible lesion, and then through the stages of tumour growth -- and subjected each stage to single-cell profiling. We identify a malignant cell state with a neural crest-like gene expression signature that is highly abundant in the early stages, but relatively diminished in the late stage of tumour growth. Genomic analysis based on the presence of copy number alterations suggests that these neural crest-like states exist as part of a heterogenous clonal hierarchy that evolves with tumour growth. By exploring the injury response in the wounded normal mouse brain, we identify cells with a similar signature that emerge following injury and then disappear over time, suggesting that activation of an injury response programme occurs during tumourigenesis. Indeed, our experiments reveal a non-malignant injury-like microenvironment that is initiated in the brain following oncogene activation in cerebral precursor cells. Collectively, our findings provide insight into the early stages of gliomagenesis, identifying a unique stem cell-like state and an injury response programme tied to early tumour formation. This will have implications on glioblastoma therapies and raises exciting new possibilities for early disease diagnosis and prevention. Some of the data in this series can also be explored through the following App link: gbm.stem-cells.ca.
2025-01-01 | GSE278511 | GEO
Project description:The lineage relationships among the hundreds of cell types generated during development are difficult to reconstruct. A recent method, GESTALT, used CRISPR–Cas9 barcode editing for large-scale lineage tracing, but was restricted to early development and did not identify cell types. Here we present scGESTALT, which combines the lineage recording capabilities of GESTALT with cell-type identification by single-cell RNA sequencing. The method relies on an inducible system that enables barcodes to be edited at multiple time points, capturing lineage information from later stages of development. Sequencing of ∼60,000 transcriptomes from the juvenile zebrafish brain identified >100 cell types and marker genes. Using these data, we generate lineage trees with hundreds of branches that help uncover restrictions at the level of cell types, brain regions, and gene expression cascades during differentiation. scGESTALT can be applied to other multicellular organisms to simultaneously characterize molecular identities and lineage histories of thousands of cells during development and disease.
2018-02-09 | GSE105010 | GEO
Project description:Due to its small and sequenced genome, short generation time, efficient transformation and increasing genetic resources, Brachypodium distachyon is an emerging model for grasses. Despite this, data capturing gene expression patterns across different organs and developmental stages is missing. We have generated a comprehensive gene expression atlas for Brachypodium, capturing 9 different organs and developmental stages
2017-06-03 | E-MTAB-5491 | biostudies-arrayexpress
Project description:The cerebral cortex plays an important role in cognitive function and specialized perception in mammals and its development requires highly specific spatio-temporal control of gene expression. The study identified stage- and region-specific markers throughout cerebral corticogenesis at various important stages of cerebral cortex development; embryonic day (E) 15.5, E17.5, postnatal day (P) 1.5 and 4-6 months old.
2009-09-25 | GSE15031 | GEO