Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [P7 cortex]

ABSTRACT: During mammalian brain development, neural stem cells (NSCs) initially produce only neurons and subsequently shift to glial production, while it is still unknown what regulates this drastic fate change. Here we discovered RNA-binding protein (RBP) of quaking (Qk) is selectively expressed in NSCs and is essential for switching from neurogenesis to gliogenesis. Using CNS-specific KO mice for Qk, we found that gliogenesis, but not neurogenesis, was specifically disrupted in Qk-/- brains. In glial differentiating condition, Qk-/- NSCs failed to enter gliogenesis but caused ectopic neurogenic gene expression. Pathway analysis of Qk-/- NSCs identified endocytosis as the regulatory functional cluster of Qk which has been shown to facilitate extra-cellular signaling receptors replacement and promote NSC differentiation. Mechanistically, Qk regulates endocytosis pathway genes through stabilizing their mRNAs via Qk binding sequences in 3’UTR. These results uncovered the cell fate determination mechanism of NSCs through mRNA regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE117016 | GEO | 2020/11/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [Dif_NSCs]

Project description:During mammalian brain development, neural stem cells (NSCs) initially produce only neurons and subsequently shift to glial production, while it is still unknown what regulates this drastic fate change. Here we discovered RNA-binding protein (RBP) of quaking (Qk) is selectively expressed in NSCs and is essential for switching from neurogenesis to gliogenesis. Using CNS-specific KO mice for Qk, we found that gliogenesis, but not neurogenesis, was specifically disrupted in Qk-/- brains. In glial differentiating condition, Qk-/- NSCs failed to enter gliogenesis but caused ectopic neurogenic gene expression. Pathway analysis of Qk-/- NSCs identified endocytosis as the regulatory functional cluster of Qk which has been shown to facilitate extra-cellular signaling receptors replacement and promote NSC differentiation. Mechanistically, Qk regulates endocytosis pathway genes through stabilizing their mRNAs via Qk binding sequences in 3’UTR. These results uncovered the cell fate determination mechanism of NSCs through mRNA regulation.

2020-11-09 | GSE117017 | GEO

RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development

Project description:RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development

| PRJNA480859 | ENA

RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [Dif_NSCs]

Project description:RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [Dif_NSCs]

| PRJNA480861 | ENA

RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [P7 cortex]

Project description:RNA-binding protein quaking (Qk) promotes switching from neurogenesis to gliogenesis of neural stem cells during brain development [P7 cortex]

| PRJNA480860 | ENA

A conserved molecular logic for neurogenesis to gliogenesis switch in the cerebral cortex [ChIP-seq]

Project description:During development neural stem cells (NSCs) in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.

2024-05-02 | GSE254690 | GEO

BET Bromodomain inhibition promotes neurogenesis while inhibiting gliogenesis in neural progenitor cells

Project description:Neural stem cells (NSCs) and progenitor cells (NPCs) are increasingly appreciated to hold great promise for regenerative medicine to treat CNS injuries and neurodegenerative diseases. However, evidence for effective stimulation of neuronal production from endogenous or transplanted NPCs for cell replacement with small molecules remains limited. To identify novel chemical entities/targets for neurogenesis, we had established a NPC phenotypic screen assay and validated it using known small-molecule neurogenesis inducers. Through screening small molecule libraries with annotated targets, we identified BET bromodomain inhibition as a novel mechanism for enhancing neurogenesis. BET bromodomain proteins, Brd2, Brd3, and Brd4 were found to be downregulated in NPCs upon differentiation, while their levels remain unaltered in proliferating NPCs. Consistent with the pharmacological study using bromodomain selective inhibitor (+)-JQ-1, knockdown of each BET protein resulted in an increase in the number of neurons with simultaneous reduction in both astrocytes and oligodendrocytes. Gene expression profiling analysis demonstrated that BET bromodomain inhibition induced a broad but specific transcription program enhancing directed differentiation of NPCs into neurons while suppressing cell cycle progression and gliogenesis. Together, these results highlight a crucial role of BET proteins as promising epigenetic regulators in NPC development and suggest a therapeutic potential of BET inhibitors in treating CNS injury and neurodegenerative diseases. NPCs were treated with (+)-JQ-1 or inactive enantiomer (-)-JQ-1 at 0.2 Î¼M or 0.5 Î¼M for 12 and 24 hrs in differentiation medium. The experiments were carried out in 3 independent preparations of NPCs (triplicates)

2016-07-24 | E-GEOD-77988 | biostudies-arrayexpress

epigenetic control of neurogenesis-to-gliogenesis switch during mouse cortical development

Project description:Gene expression and chromatin accessiblity changes as cortical RG switch from neurogenesis to gliogenesis; the bivalent chromatin present in the temporally upregulated genes maintain them poised.

2023-06-08 | GSE234101 | GEO

Gliogenesis in Drosophila

Project description:In Drosophila, the glial cells missing (gcm) gene encodes a transcription factor that controls the determination of glial versus neuronal fate. In gcm mutants, presumptive glial cells are transformed into neurons and, conversely, when gcm is ectopically misexpressed, presumptive neurons become glia. Although gcm is thought to initiate glial cell development through its action on downstream genes that execute the glial differentiation program, little is known about the identity of these genes. To identify gcm downstream genes in a comprehensive manner, genome-wide oligonucleotide arrays were used to analyze differential gene expression in wild-type embryos versus embryos in which gcm is misexpressed throughout the neuroectoderm. Transcripts were analyzed at two defined temporal windows during embryogenesis. This first genome-wide analysis of gene expression events downstream of a key developmental transcription factor presents a novel level of insight into the repertoire of genes that initiate and maintain cell fate choices in CNS development. Keywords: other

2003-02-04 | GSE276 | GEO

BET Bromodomain inhibition promotes neurogenesis while inhibiting gliogenesis in neural progenitor cells

2016-07-24 | GSE77988 | GEO

Palmitoylation of BMPR1a regulates neural stem cell fate

Project description:Neural stem cells (NSCs) generate neurons and glial cells throughout embryonic and postnatal brain development. The role of s-acylation, a reversible post-translational lipid modification of proteins, in regulating fate and activity of NSCs remains largely unknown. We here used an unbiased screening approach to identify proteins that are s-acylated in mouse NSCs.

2019-11-27 | PXD014355 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data