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Lysosomal Dynamics Orchestrate Neurogenesis [Polysome-seq]

ABSTRACT: Lysosomes are cellular recycling stations and metabolic signaling hubs. Whether lysosome dynamics regulate mammalian brain development is unknown. We found that radial glia cells possess a large number of endolysosomes and that asymmetric inheritance of lysosomes in daughters of radial glia cells can predict fate and cell cycle length. To determine the translation control by the mTORC1, we performed polysome profiling of mRNAs associated with >3 ribosomes for neural progenitor cells that treated with DMSO or Torin1 for 2 hours.

ORGANISM(S): Mus musculus

PROVIDER: GSE205681 | GEO | 2022/08/31

REPOSITORIES: GEO

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Lysosomal Dynamics Orchestrate Neurogenesis [RIP-Seq]

Project description:Lysosomes are cellular recycling stations and metabolic signaling hubs. Whether lysosome dynamics regulate mammalian brain development is unknown. We found that radial glia cells possess a large number of endolysosomes and that asymmetric inheritance of lysosomes in daughters of radial glia cells can predict fate and cell cycle length. To determine the lysosomal regulation of translation initiation by mTORC1/eIF4E axis, we performed RNA immunoprecipitation sequencing (RIP-seq) with antibody against eIF4E in E13.5 neocortex.

2022-08-31 | GSE205683 | 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

Prospective isolation of functionally distinct radial glial subtypes - lineage and transcriptome analysis

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.

2008-05-29 | GSE8034 | GEO

Lysosomal Dynamics Orchestrate Neurogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-31 | GSE205685 | GEO

Crohn's disease risk variant in GPR65 alters lysosomal function

Project description:Using an siRNA screen we identify a role for GPR65 in the defense against intracellular pathogens. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria as well as an accumulation of aberrant phagosomes and lysosomes. Transcriptional profiling revealed changes in genes associated with lysosomal function. Bone marrow-derived macrophages from WT or Gpr65-/- mice were harvested for RNA analysis.

2016-06-15 | E-GEOD-69445 | biostudies-arrayexpress

Low H3K27me3 define poorly prognostic pediatric posterior fossa ependymomas

Project description:A subgroup of Posterior fossa ependymomas show reduced H3K27me3 are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin.

2016-11-23 | GSE89451 | GEO

Single cell sequencing of radial glia progeny reveals diversity of newborn neurons in the adult zebrafish brain

Project description:Zebrafish display widespread and pronounced adult neurogenesis, which is fundamental for their regeneration capability after central nervous system injury. However, the cellular identity and the biological properties of adult newborn neurons are elusive for most brain areas. Here, we used short-term lineage tracing of radial glia progeny to prospectively isolate newborn neurons from the her4.1+ radial glia lineage in the homeostatic adult forebrain. Transcriptome analysis of radial glia, newborn neurons and mature neurons using single cell sequencing identified distinct transcriptional profiles including novel markers for each population. Specifically, we detected 2 separate newborn neuron types, which showed diversity of cell fate commitment and location. Further analyses showed homology of these cell types to neurogenic cells in the mammalian brain, identified neurogenic commitment in proliferating radial glia and indicated that glutamatergic projection neurons fate are generated in the adult zebrafish telecephalon. Thus, we prospectively isolated adult newborn neurons from the adult zebrafish forebrain, identified markers for newborn and mature neurons in the adult brain, revealed intrinsic heterogeneity among adult newborn neurons and their homology to mammalian adult neurogenic cell types.

2019-11-27 | GSE137525 | GEO

Global reduction in H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

Project description:A subgroup of Posterior fossa ependymomas show reduced H3K27me3, global DNA hypomethylation, are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin.

2016-11-23 | GSE89448 | GEO

Low H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

2016-11-23 | GSE89446 | GEO

DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas

Project description:A subset of genomically silent childhood posterior fossa ependymomas show reduced H3K27me3, global DNA hypomethylation, are more invasive, exhibit poor prognosis and epigenetically deregulated genes converge on radial glial factors, suggesting developing cerebellar radial glia as candidate cells-of-origin.

2016-11-28 | GSE87779 | GEO

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