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Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Nanostring]

ABSTRACT: Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Nanostring]

PROVIDER: PRJNA806894 | ENA |

REPOSITORIES: ENA

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Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Project description:Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed an integrated clinicogenomic analysis of 36 AB-like tumors. Lesions with MN1-BEND2 fusions demonstrated decreased promoter methylation and increased expression of IGF2-H19 and DLK1-DIO3 imprinted region genes. They also relatively overexpressed genes highly expressed during fetal brain development prior to 25 post-conception weeks (pcw), including genes enriched in ventricular zone radial glia (vRG), and generally presented in young children. Other tumors highly expressed MAP kinase pathway, PI3K pathway and X-inactivation escape genes. These and a third group of tumors tended to occur in young adults and showed enriched expression of outer radial glia (oRG) and truncated radial glia (tRG) genes, and genes highly expressed after 25 pcw. Many of the latter are involved in axonal migration or synaptic plasticity and are implicated in autism, schizophrenia and other cognitive disorders. Findings suggest that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors during fetal and later brain development: early ependymal tumors with MN1-BEND2 fusions (EET-MN1) from vRG-derived progenitor cells, and MAPK/PI3K and classic astroblastomas from oRG- and tRG-derived progenitors, respectively. Lastly, we found that like EET-MN1, immature ependymal cells express IGF2 and may represent an important source of this growth factor in the fetal lateral ventricular zone neural stem cell niche.

2022-02-20 | GSE165351 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [methylation]

2022-02-20 | GSE166569 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Affymetrix]

2022-02-20 | GSE165813 | GEO

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Project description:Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

| PRJNA694144 | ENA

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [methylation]

Project description:Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [methylation]

| PRJNA701290 | ENA

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Affymetrix]

Project description:Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Affymetrix]

| PRJNA697956 | ENA

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Project description:Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively. Tumors with MN1-BEND2 fusion appear to present exclusively in females and exhibit overexpression of genes expressed prior to 25 post-conception weeks (pcw), including genes enriched in early ventricular zone radial glia and ependymal tumors. Other, histologically classic ABs overexpress or harbor mutations of mitogen-activated protein kinase pathway genes, outer and truncated radial glia genes, and genes expressed after 25 pcw, including neuronal and astrocyte markers. Findings support that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors. Selective gene fusion, variable imprinting and/or chromosome X-inactivation escape resulting in biallelic overexpression may contribute to female predominance of AB molecular subtypes.

| S-EPMC9018799 | biostudies-literature

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes [Nanostring]

Project description:Astroblastoma (AB) is an unusual brain tumor of unknown origin. We performed a clinicogenomic analysis of AB-like tumors.

2022-02-20 | GSE196697 | GEO

Transcription profiling of mouse functionally distinct radial glial subsets

Project description:Since the discovery of radial glia as the source of neurons, their heterogeneity in regard to neurogenesis has been described by clonal and time-lapse analysis in vitro. However, the molecular determinants specifying neurogenic radial glia differently from radial glia that mostly self-renew remain ill-defined. Here, we isolated two radial glial subsets that co-exist at mid-neurogenesis in the developing cerebral cortex and their immediate progeny. While one subset generates neurons directly, the other is largely non-neurogenic but also gives rise to Tbr2-positive basal precursors, thereby contributing indirectly to neurogenesis. Isolation of ; these distinct radial glia subtypes allowed determining interesting differences in their transcriptome. These transcriptomes were also strikingly different from the transcriptome of radial glia isolated at the end of neurogenesis. This analysis therefore identifies, for the first time, the lineage origin of basal progenitors and the molecular differences of this lineage in comparison to directly neurogenic and gliogenic radial glia. Experiment Overall Design: Comparison of radial glial subtypes

2008-06-18 | E-GEOD-8034 | biostudies-arrayexpress

Generation of cellular diversity through temporal patterning of radial glia during mouse corticogenesis

Project description:Neural cell type diversity arises from both spatial and temporal patterning of neural stem cells. Although spatial patterning mechanisms have been extensively studied, temporal patterning mechanisms remain relatively unexplored. In this study, we addressed generation of diverse neural cell types through lineage progression of mouse cortical radial glia. The time series scRNA-seq and snATAC-seq of mouse cortical development revealed that radial glia temporally transitioned from neurogenesis to gliogenesis. During gliogenic stages, various cell types were generated simultaneously along multidirectional lineage trajectories. We established comprehensive molecular maps for cortical lineage commitment and cellular diversification. The transcriptome and epigenome of cortical radial glia exhibit temporal dynamics, as revealed by scRNA-seq and snATAC-seq. Lhx2, a transcription factor with temporal dynamic chromatin binding activities, was identified as a key regulator of the neurogenesis-to-gliogenesis transition. It maintains neurogenic competence by establishing the active epigenetic state of its target genes.

2024-09-03 | GSE276209 | GEO

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